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Review ArticleReview Article
Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Antonio Inserra, Danilo De Gregorio and Gabriella Gobbi
Michael Nader, ASSOCIATE EDITOR
Pharmacological Reviews January 2021, 73 (1) 202-277; DOI: https://doi.org/10.1124/pharmrev.120.000056
Antonio Inserra
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada
Danilo De Gregorio
Gabriella Gobbi
Michael Nader
Roles: ASSOCIATE EDITOR
Article Figures & Data
Neuroplastic effects of psychedelic compounds relevant to psychiatric disorders and comorbidities. The main outcomes elicited by psychedelic compounds on neuroplastic and neurogenesis-related pathways are reported in the green box (purple brain). The resulting outcomes on psychiatric symptoms are reported in the blue box (orange brain). For each compound, or group of compounds with similar pharmacology, the main classes of transcription factors and signaling pathways activated that are thought to mediate the effects of the compound on synaptic and neuronal plasticity are reported. In the bottom part of the figure, the main receptors involved in signal transduction for each compound or group of compounds with similar pharmacology and the resulting neurotransmitter released are reported. AR, androgen receptor; ALT, alternative lengthening of telomeres; ANIA3, activity and neurotransmitter-induced early gene 3; CAMK2, calcium/calmodulin-dependent protein kinase 2; CEBPB, CCAAT/enhancer-binding protein beta; COMT, catechol O-methyltransferase; CREB, cAMP response element-binding protein; MKP1, mitogen-activated protein kinase phosphatase; NOR1, neuron-derived orphan receptor-1; IKB, inhibitor of kB kinase.
Anti-inflammatory and immunomodulatory effects of psychedelic compounds relevant to psychiatric disorders and comorbidities. The main outcomes elicited by psychedelic compounds on inflammation and immunity-related pathways are reported in the blue box (purple brain). The resulting outcomes on psychiatric symptoms are reported in the purple box (orange brain). For each compound, or group of compounds with similar pharmacology, the main classes of cytokines, chemokines, hormones, transcription factors, and signaling pathways activated, which are thought to mediate the effects of the compound on inflammation and immunity-related pathways, are reported. In the bottom part of the figure, the main receptors involved in signal transduction for each compound or group of compounds with similar pharmacology and the resulting neurotransmitter released are reported. ADRA, alpha adrenergic receptor; ADRB, beta adrenergic receptor; ALPHA2, alpha 2 adrenergic receptor; CCL5, C-C motif chemokine 5; CORT, cortisol; CX3CL1, fractalkine; CXCL10, C-X-C motif chemokine 10; GLU, glutamate; HRH, histamine receptor; I1, imidazoline receptor 1; IKBA, NF-kappa-B inhibitor alpha; ICAM1, intercellular adhesion molecule 1; M3, muscarinic receptor subtype 3; M5, muscarinic receptor subtype 5; SIGMAR, sigma receptor; TAAR, trace amine-associated receptor; TLR, toll-like receptor; TSH, thyroid stimulating hormone; VCAM1, vascular cell adhesion protein 1.
Effects of psychedelic compounds on the serotonergic, dopaminergic, glutamatergic, and GABAergic neurotransmitter systems relevant to psychiatric disorders and comorbidities. For each compound, or group of compounds with similar pharmacology, the main known modulatory effects over the serotonergic, dopaminergic, glutamatergic, and GABAergic neurotransmitter systems in different areas of the brain are reported.
Clinical trials available on ClinicalTrials.gov investigating the use of MDMA as a potential therapeutic approach for PTSD and other psychiatric disorders
For completed trials, the references of published work were added if available either from the ClinicalTrials.gov web site or PubMed upon searching the NCT identifier. If information was available on the main findings of the study, it was added. If the trial was not completed or it was completed but no information was available in the form of a published original manuscript, we reported the main research question(s) the study aims to address.
Cohort
Research Question/Main Findings
MDMA Post-traumatic stress disorder 30, 75, or 125 mg, orally, followed by a supplemental half dose 1.5–2 h later, thrice MDMA-assisted psychotherapy is safe and efficacious for PTSD. MDMA induces large-magnitude effect size decreases in PTSD symptoms. Two-thirds of participants no longer meet PTSD criteria 12 mo after treatment Completed ClinicalTrials.gov identifier: NCT03485287, NCT03282123, NCT01211405 (Mithoefer et al., 2018; Gorman et al., 2020)
MDMA Post-traumatic stress disorder 125 mg, orally, followed by a supplemental half dose 1.5–2 h later, thrice Decrease in PTSD scores. Rate of clinical response 10 of 12 (83%) in the active treatment group vs. 2 of 8 (25%) in the placebo group. No drug-related serious adverse events or clinically significant blood pressure increases. No relapse 17–74 mo after the original final session Completed ClinicalTrials.gov identifier: NCT00090064 (Mithoefer et al., 2011, 2013)
MDMA Post-traumatic stress disorder 30, 75, or 125 mg, orally, followed by a supplemental half dose 1.5–2 h later, once Identify psychotherapeutic processes in MDMA-assisted psychotherapy for PTSD Completed ClinicalTrials.gov identifier: NCT02102802
MDMA Post-traumatic stress disorder 25 or 125 mg, orally, followed by a supplemental half dose 2 h later, thrice Safety and efficacy of MDMA-assisted psychotherapy for PTSD Completed ClinicalTrials.gov identifier: NCT01958593, NCT01689740
MDMA Post-traumatic stress disorder 62.5, 125, or 125 + 62.5 mg, orally Additional MDMA psychotherapy for people who relapsed 1 yr after the first trial Completed ClinicalTrials.gov identifier: NCT01458327
MDMA War- or terrorism-related PTSD 25 and 125 mg, orally, followed by a supplemental half dose 2–2.5 h later, twice MDMA-assisted psychotherapy for people with war- or terrorism-related PTSD Terminated due to staff turnover and its effects on data collection ClinicalTrials.gov identifier: NCT00402298
MDMA Post-traumatic stress disorder 1.5 mg/kg, orally, once Effects of MDMA on prefrontal and amygdala activation. Relationship between neural changes and acute behavioral effects in patients with PTSD Recruiting ClinicalTrials.gov identifier: NCT03752918
MDMA Post-traumatic stress disorder 80 and 120 mg, orally, followed by a supplemental half dose 1.5–2 h later, thrice Multisite phase III study of MDMA-assisted psychotherapy for PTSD Active, not recruiting ClinicalTrials.gov identifier: NCT03537014
MDMA Post-traumatic stress disorder 80 and 120 mg, orally, followed by a supplemental half dose 1.5–2 h later, twice First multisite study of MDMA-assisted psychotherapy for PTSD in Europe. Exploration of findings' reproducibility from FDA-regulated trials in a multisite format to further confirm the phase III study design Not yet recruiting ClinicalTrials.gov identifier: NCT04030169
MDMA Combat-related post-traumatic stress disorder First session: 80 mg, orally, followed by a supplemental half dose 1.5–2 h later; second and third sessions: 120 mg, orally, followed by a supplemental half dose 1.5–2 h later Efficacy of MDMA-assisted psychotherapy in veterans with combat-related, refractory PTSD Not yet recruiting ClinicalTrials.gov identifier: NCT04264026
MDMA CBCT in dyads with one member with post-traumatic stress disorder First session: 75 mg, orally, followed by a supplemental half dose 1.5 h later; second session: 75 or 100 mg, orally, followed by a supplemental half dose 1.5 h later Safety and effect size of a combination of CBCT and MDMA-assisted psychotherapy in 10 pairs of people, one with and one without PTSD. Changes in PTSD symptoms and relationship issues before and after the course of psychotherapy Completed ClinicalTrials.gov identifier: NCT02876172
MDMA Autism spectrum disorder First session: 75 or 100 mg, orally; second session: 100 or 125 mg MDMA-assisted psychotherapy is safe and elicits rapid and durable therapeutic improvements in social anxiety symptoms in adults with ASD Completed ClinicalTrials.gov identifier: NCT02008396 (Danforth et al., 2018)
MDMA Autism spectrum disorder 1.5 mg/kg, orally Assess whether MDMA affects the response to affective touch in individuals with a range of autistic traits and healthy volunteers Recruiting ClinicalTrials.gov identifier: NCT04053036, NCT03790618
Substance, Alcohol, and Tobacco Abuse
MDMA Alcohol use disorder 125 mg, orally, followed by a supplemental half dose 2 h later, twice Feasibility of MDMA-assisted psychotherapy in patients with AUD who have recently undergone detoxification Active, not recruiting ClinicalTrials.gov identifier: NCT04158778
MDMA Substance abuse disorder 125 mg, orally, once Oxytocin receptor gene variants may modulate aspects of the prosocial effects of MDMA. MDMA produces significantly greater feelings of trust in rs1042778 TT genotypes compared with G allele carriers. MDMA significantly increases plasma oxytocin. MDMA and oxytocin plasma concentrations do not differ among oxytocin genetic variants Completed ClinicalTrials.gov identifier: NCT01270672 (Vizeli and Liechti, 2018)
MDMA Substance abuse disorder 125 mg, orally, once Effects of MDMA on social and emotional processing Completed ClinicalTrials.gov identifier: NCT01465685 (Hysek et al., 2014; Vizeli and Liechti, 2018)
MDMA Substance abuse disorder 1.6 mg/kg, orally, once Evaluate the effects of MDMA on thinking and the relationship between plasma MDMA levels and brain function (fMRI) Completed ClinicalTrials.gov identifier: NCT01148342
MDMA Life-threatening illness 125 mg, orally, followed by a supplemental half dose 1.25–2.5 later, thrice Safety and efficacy of MDMA-assisted psychotherapy in people with anxiety related to a life-threatening cancer or neurologic illness. Effects of MDMA on neural correlates of emotional processing and anxiety Completed ClinicalTrials.gov identifier: NCT02427568, NCT02954562
MDMA Hepatic impairment 80 mg, orally, once Assess the effect of moderate hepatic impairment in the pharmacokinetics of MDMA and its active metabolite MDA to decide whether dosage adjustment is required for moderate hepatic impairment Recruiting ClinicalTrials.gov identifier: NCT03606538
MDMA Recreational users Depending on self-administration Ecstasy use is associated with tissue changes in the globus pallidus. Lower cortical postsynaptic 5-HT2A in recent users. Higher 5-HT2A in the occipital cortex of ex-MDMA users. MDMA abuse associated with neuronal damage. Greater MDMA abuse associated with higher depressive scores. No decrease in SERT density in former MDMA abusers Completed ClinicalTrials.gov identifier: NCT00235768 (Reneman et al., 2001a,b, 2002b; de Win et al., 2004)
MDMA Recreational users Depending on self-administration MDMA users report somatic complaints on day 1, and symptoms of reduced energy, increased fatigue, and weakness persisted up to 4 days post–drug ingestion Completed ClinicalTrials.gov identifier: NCT01400204
MDMA Healthy volunteers 1.5 mg/kg, orally, once Female subjects experience more intense physiologic (heart rate and oral temperature) and negative effects (dizziness, sedation, depression, and psychotic symptoms). Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/*) determine greater cardiovascular effects, and (met/* or s/s) determines negative subjective effects (dizziness, anxiety, sedation). MDMA inhibits CYP2D6 activity. Recovery of CYP2D6 activity half-life 46.6 h. Full recovery after 10 days Completed ClinicalTrials.gov identifier: NCT01447472 (O'Mathuna et al., 2008; Yubero-Lahoz et al., 2011; Pardo-Lozano et al., 2012)
MDMA Healthy volunteers 125 mg, orally, once Dopamine and norepinephrine transporter-mediated release of norepinephrine is involved in MDMA cardiostimulant effect. No modulatory role of dopamine. MDMA during bupropion therapy may result in higher plasma concentrations and enhanced mood effects but also lower cardiac stimulation. Genetic polymorphisms of the norepinephrine SLC6A2 gene weakly moderates the cardiovascular response to MDMA and may play a minor role in adverse cardiovascular events Completed ClinicalTrials.gov identifier: NCT01771874 (Schmid et al., 2015b; Steuer et al., 2015; Vizeli et al., 2018)
MDMA Healthy volunteers 125 mg, orally, once MDMA increases oxytocin but not BDNF plasma levels. No association between interindividual variations in the acute effects of MDMA in humans and DA system gene variants Completed ClinicalTrials.gov identifier: NCT03019822 (Vizeli and Liechti, 2019; Holze et al., 2020)
MDMA Healthy volunteers 125 mg, orally, once MDMA-induced prolongation of the latency to and reduction of light-induced miosis indicate indirect central parasympathetic inhibition, and the faster recovery time reflects an increased sympathomimetic action Completed ClinicalTrials.gov identifier: NCT00886886 (Hysek and Liechti, 2012)
MDMA Healthy volunteers 125 mg, orally, once α1-Adrenergic receptor contributes to the acute cardiostimulant effects of MDMA Completed ClinicalTrials.gov identifier: NCT01386177 (Hysek et al., 2013)
MDMA Healthy volunteers 125 mg, orally, once The combined use of methylphenidate and MDMA enhances cardiovascular and adverse effects Completed ClinicalTrials.gov identifier: NCT01465685 (Hysek et al., 2014)
MDMA Healthy volunteers 125 mg, orally, once The 5-HT and NE transporter inhibitor duloxetine inhibits MDMA effects (may be useful in the treatment of psychostimulant dependence). MDMA increases copeptin, a marker for arginine vasopressin hormone secretion, in women but not in men. This may explain higher hyponatremia frequency in females Completed ClinicalTrials.gov identifier: NCT00990067 (Simmler et al., 2011; Hysek et al., 2012b)
MDMA Healthy volunteers 125 mg, orally, once MDMA produces pupil dilation, subjective good drug effects, drug liking, happiness, and trust. MDMA reduces subjective anxiety and fear. MDMA produces sexual arousal-like effects. MDMA increases cortisol, prolactin, and oxytocin Completed ClinicalTrials.gov identifier: NCT01951508 (Dolder et al., 2018)
MDMA Healthy volunteers 1.5 mg/kg, orally, once Investigate the effects of serotonin release in the subjective effects of MDMA Completed ClinicalTrials.gov identifier: NCT00838305
MDMA Healthy volunteers 1.6 mg/kg, orally, once Investigated the interactive effects of the β-blocker pindolol with MDMA on heart rate, blood pressure, body temperature, and adverse effects Completed ClinicalTrials.gov identifier: NCT00895804
MDMA Healthy volunteers 1 mg/kg, orally, once Assess the effects of MDMA on encoding and retrieval of emotional and social memories when the drug is administered before encoding and before retrieval Completed ClinicalTrials.gov identifier: NCT03050541
MDMA Healthy volunteers 100 mg, orally, once Assess the effects of MDMA on startle response and fear conditioning. Measurement of blood BDNF, oxytocin, and cortisol. Assess the effects of MDMA on sleep Recruiting ClinicalTrials.gov identifier: NCT03181763
MDMA Healthy volunteers 125 mg, orally, once Assess the role of MDMA-induced acute serotonin release in the effects of fear extinction Recruiting ClinicalTrials.gov identifier: NCT03527316
MDMA Healthy volunteers 125 mg, orally, followed by a supplemental half dose 1.25–2.5 h later, once Assess the effects of MDMA on therapists trained to perform MDMA-assisted psychotherapy research Enrolling by invitation ClinicalTrials.gov identifier: NCT01404754
MDMA Healthy volunteers 0.75–1.5 mg/kg, orally, once Assess the effects of MDMA on the functioning of reward-related brain circuits (fMRI) Not yet recruiting ClinicalTrials.gov identifier: NCT04060108
MDMA Healthy volunteers N/A Effects of MDMA on mood and cognitive performance Completed ClinicalTrials.gov identifier: NCT02033707
MDMA Healthy volunteers 120 mg, orally, followed by a supplemental half dose 1.5–2 h later, once Collect information to support the safety profile of MDMA-assisted psychotherapy. Understand acute effects for use in therapy Not yet recruiting ClinicalTrials.gov identifier: NCT04073433
AUD, alcohol use disorder; CBCT, cognitive behavioral conjoint therapy; COMT, catechol O-methyltransferase; fMRI, functional magnetic resonance imaging; N/A, not available; NCT, ClinicalTrials.gov identifier; SLC6A2, sodium-dependent noradrenaline transporter; 5-HTTLPR, serotonin transporter-linked polymorphic region.
Clinical trials available on ClinicalTrials.gov investigating the use of psilocybin as a potential therapeutic approach for MDD and other psychiatric disorders
For completed trials, the references of the published work were added if available either from the ClinicalTrials.gov web site or PubMed upon searching the NCT identifier. If information was available on the main findings of the study, it was added. If the trial was not completed or it was completed but no information was available in the form of a published original manuscript, we reported the main research question(s) the study aims to address.
Psilocybin Major depressive disorder First session: 0.3 mg/kg, orally; second session (after 2 wk from first): 0.45 mg/kg, orally; third session (after 4 wk from second): 0.6 mg/kg, orally Pharmacokinetics study. No physical or psychological adverse events within 30 days of any dose. The dose of 0.6 mg/kg might be in excess of therapeutic dose. No psilocybin found in plasma or urine. Renal clearance of intact psilocin 2%. No dose reduction needed for subjects with mild to moderate renal impairment. High-dose psilocybin is associated with positive subjective effects in healthy volunteers Completed ClinicalTrials.gov identifier: NCT02163707 (Brown et al., 2017b; Nicholas et al., 2018)
Psilocybin Treatment-resistant depression First session: 10 mg; second session: 25 mg (7 days apart) Treatment is well tolerated. No major adverse events. Transient anxiety, confusion, mild nausea, and headache. Psychological support recommended before, during, and after the session. Depressive symptoms reduced 1 wk, 5 wk, and 3 mo after psilocybin. Marked improvements in anxiety and anhedonia. Quality of the acute experience predicts the reduction in depressive scores Completed Carhart-Harris et al., 2016a, 2018
Psilocybin Treatment-resistant depression First session: 10 mg; second session: 25 mg (7 days apart) Psilocybin (post-treatment) decreases cerebral blood flow in the temporal cortex and amygdala. Decreased amygdala activity correlates with the antidepressant effect of psilocybin. Increased functional connectivity between ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex and decreased functional connectivity between parahippocampus-PFC predicts treatment response at 5 wk Completed Carhart-Harris et al., 2017
Psilocybin Treatment-resistant depression First session: 10 mg; second session: 25 mg (7 days apart) Increased emotional responses to happy and fearful faces in the right amygdala after treatment. Psilocybin revives emotional responsiveness in patients with TRD Completed Roseman et al., 2018
Psilocybin Treatment-resistant depression First session: 10 mg; second session: 25 mg (7 days apart) Psilocybin treatment decreases authoritarianism and increases nature relatedness Completed Lyons and Carhart-Harris, 2018
Psilocybin Major depressive disorder 0.215 mg/kg, orally, once Effects on depressive symptoms and brain functioning (fMRI) Recruiting ClinicalTrials.gov identifier: NCT03715127
Psilocybin Major depressive disorder 25 mg, orally, once Potential efficacy of a single 25-mg oral dose of psilocybin for MDD Recruiting ClinicalTrials.gov identifier: NCT03866174
Psilocybin Major depressive disorder 0.1 and 0.3 mg/kg, orally, twice Assess whether psilocybin enhances neuroplasticity in MDD patients (EEG + long-term potentiation task) Recruiting ClinicalTrials.gov identifier: NCT03554174
Psilocybin Major depressive disorder 25 mg, orally, once Long-term (up to 24 mo) follow-up study of patients with MDD who previously received psilocybin Enrolling by invitation ClinicalTrials.gov identifier: NCT04353921
Psilocybin Major depressive disorder Moderate/high dose (dose N/A) Acute and persisting effects of psilocybin on depressive symptoms and other moods, attitudes, and behavior Active, not recruiting ClinicalTrials.gov identifier: NCT03181529
Psilocybin Major depressive disorder Multiple dosing days (dose and frequency N/A) Comparing antidepressant action and mechanisms of action of psilocybin and the SSRI escitalopram (fMRI) Active, not recruiting ClinicalTrials.gov identifier: NCT03429075
Psilocybin Major depressive disorder 25 mg, orally, once Long-term therapeutic effects of psilocybin (fMRI, peripheral gene expression and molecules as predictor biomarkers of treatment outcome) Not yet recruiting ClinicalTrials.gov identifier: NCT03380442
Psilocybin MDD with mild cognitive impairment or early Alzheimer disease First session: 15 mg/70 kg; second session (2 wk after): 15 or 25 mg/70 kg Safety and efficacy of psilocybin given under supportive conditions in depressed people with MCI or early AD. Follow-up assessment of long-term therapeutic effects Recruiting ClinicalTrials.gov identifier: NCT04123314
Psilocybin Treatment-resistant depression Low, medium, high dose (dose and frequency N/A) Safety and efficacy of psilocybin in patients with TRD Recruiting ClinicalTrials.gov identifier: NCT03775200
Alcohol, Tobacco, and Substance Use Disorder
Psilocybin Alcohol use disorder 0.3–0.4 mg/kg, orally, twice Abstinence increased after psilocybin. Gains maintained at 36 wk. Experience intensity in the first psilocybin session predicts decreases in drinking and craving and increases in abstinence. No significant treatment-related adverse events Active, not recruiting ClinicalTrials.gov identifier: NCT02061293 (Bogenschutz et al., 2015; Nielson et al., 2018)
Psilocybin Alcohol use disorder 25 mg, orally, once Clinical and mechanistic effects of psilocybin in patients with alcohol addiction (3- and 6-mo follow-up) Not yet recruiting ClinicalTrials.gov identifier: NCT04141501
Psilocybin Opioid use disorder Two doses 4 wk apart, orally (dose N/A) Psilocybin augmentation of buprenorphine/naloxone maintenance therapy for OUD with guided counseling. Assess changes in pain and life quality Not yet recruiting ClinicalTrials.gov identifier: NCT04161066
Psilocybin Tobacco use disorder 20 and 30 mg/70 kg, once Comparing psilocybin to transdermal nicotine patch in individuals seeking to quit smoking (3-, 6-, and 12-mo follow-up). Previous trial: 80% abstinence after 7 days, 67% abstinence at 12- mo follow-up. Psilocybin experiences among the five most personally meaningful and spiritually significant experiences of participants' lives Recruiting ClinicalTrials.gov identifier: NCT01943994 (Garcia-Romeu et al., 2014; Johnson et al., 2014, 2017)
Psilocybin Cocaine use disorder 0.36 mg/kg, orally, once Feasibility and efficacy of psilocybin-facilitated treatment of cocaine use. Impact of psilocybin-facilitated treatment on other drug use and outcomes relevant to cocaine involvement (such as criminal involvement). Default mode network changes investigated by fMRI Recruiting ClinicalTrials.gov identifier: NCT02037126
Psilocybin Obsessive-compulsive disorder 0.25 mg/kg, orally, once Investigate neural mechanisms underpinning OCD symptom improvements by psilocybin (fMRI) Recruiting ClinicalTrials.gov identifier: NCT03356483
Psilocybin Obsessive-compulsive disorder 0.1 and 0.3 mg/kg, orally, once weekly for 8 wk Safety, tolerability, and mechanism of action of psilocybin (and the anxiolytic lorazepam) as OCD treatments. Functional connectivity changes between the caudate nucleus and orbital frontal cortex Recruiting ClinicalTrials.gov identifier: NCT03300947 (Moreno et al., 2006)
Patients with Cancer
Psilocybin Potentially life-threatening cancer 1–3 or 22–30 mg/kg, orally, twice Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer. Improved quality of life, life meaning, and optimism and decreases in death anxiety. Changes sustained at 6-mo follow-up in 80% of participants. Improvements in attitudes about life/self, mood, relationships, and spirituality. Increased well-being/life satisfaction Completed ClinicalTrials.gov identifier: NCT00465595 (Griffiths et al., 2016)
Psilocybin Potentially life-threatening cancer 0.2 mg/kg, orally, once Reduction in anxiety scores at 1 and 3 mo and improvements in depression scores at 6 mo Completed ClinicalTrials.gov identifier: NCT00302744 (Grob et al., 2011)
Psilocybin Potentially life-threatening cancer 0.3 mg/kg, orally, once Immediate, substantial, and sustained improvements in anxiety and depression. Decreases in cancer-related demoralization and hopelessness, improved spiritual well-being, and increased quality of life. Enduring anxiolytic and antidepressant effects and reductions in depression and anxiety at 6-mo follow-up in 60%–80% of patients. Sustained benefits in existential distress and quality of life and improved attitudes toward death. Psilocybin-occasioned mystical experiences mediate the therapeutic effects on anxiety and depression Active, not recruiting ClinicalTrials.gov identifier: NCT00957359 (Ross et al., 2016)
Psilocybin Anorexia nervosa First session: the lesser of 20 mg or 0.6 mg/kg; second session: the lesser of 25 mg or 0.6 mg/kg. Assess the safety and efficacy of moderate- to high-dose psilocybin in people suffering from AN. Assess whether long-term positive behavioral changes (eating habits, anxiety, and depression) can be elicited in a supportive setting with close follow-up. Assess whether psilocybin decreases eating disorder pathophysiology Recruiting ClinicalTrials.gov identifier: NCT04052568
Psilocybin AIDS survivors Once, orally (dose N/A) Safety, tolerability, and feasibility of psilocybin-assisted group therapy for demoralization in long-term AIDS survivors. Effects on demoralization, complicated grief, anxiety, life quality, functional social support, post-traumatic growth, openness to experience, mindfulness, social connection, nature relatedness, and medication adherence Completed ClinicalTrials.gov identifier: NCT02950467
Psilocybin Long-term meditators Once or twice, dose manipulation (dose N/A) Characterize performance of tasks, brain functioning, and the effects of psilocybin in long-term meditators. Psychological function, behavioral and cognitive tasks, brain resting-state functional connectivity Completed ClinicalTrials.gov identifier: NCT01988311
Psilocybin Long-term meditators Very low dose, moderately low dose, moderately high dose (dose N/A) Acute and persisting effects of psilocybin on meditation, spirituality, health, well-being, prosocial attitudes, and brain functioning (fMRI) Completed ClinicalTrials.gov identifier: NCT02145091
Religious Professional Leaders
Psilocybin Religious professional leaders First session: 20 mg/70 kg, orally; second session: 20 or 30 mg/70 kg, orally Utility of psilocybin for professional religious leaders. Further understanding of mystical-type experiences. Changes in psychological functioning, spirituality, health, well-being, and prosocial attitudes Recruiting ClinicalTrials.gov identifier: NCT02421263
Psilocybin Religious professional leaders First session: 20 mg/70 kg, orally; second session: 20 or 30 mg/70 kg, orally Effects and utility of psilocybin-facilitated experiences for professional religious leaders Recruiting ClinicalTrials.gov identifier: NCT02243813
Psilocybin Healthy volunteers 25 mg/70 kg, orally, once Reduction of negative affect and amygdala response to facial affect stimuli at 1 wk postpsilocybin. Increase in positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally conflicting stimuli after 1 wk. Negative affective and amygdala response to facial affect stimuli back to baseline after 1 mo, whereas positive affect remains elevated, and trait anxiety reduced. Increased resting-state functional connectivity at 1 wk and 1 mo postpsilocybin. Psilocybin may increase emotional and brain plasticity, and negative affect may be targeted with psilocybin Completed ClinicalTrials.gov identifier: NCT02971605 (Barrett et al., 2020)
Psilocybin Healthy volunteers 2 mg by i.v. infusion, once Profound changes in consciousness. Decreased BOLD fMRI signals in thalamus, anterior and posterior cingulate cortex, and mPFC. Decrease in positive coupling between the mPFC and PCC. Psychedelics may induce a state of "unrestrained cognition" Completed Carhart-Harris et al., 2012
Psilocybin Healthy volunteers 2 mg by i.v. infusion, once Psilocybin increases DMN-TPN functional connectivity, as observed in psychosis and meditative states. Thalamocortical functional connectivity not affected Completed Carhart-Harris et al., 2013
Psilocybin Healthy volunteers 2 mg by i.v. infusion, once During the psychedelic state, the brain biases a mode of whole-brain functional integration at the expense of local networks Completed BioRxiv 10.1101/376491v1
Psilocybin Healthy volunteers 2 mg by i.v. infusion, once The subjective effects of psilocybin might arise as a result of cortical oscillatory rhythm desynchronization, potentially arising from the stimulation of deep-layer 5-HT2A receptors on pyramidal neurons Completed Muthukumaraswamy et al., 2013
Psilocybin Healthy volunteers 2 mg by i.v. infusion, once Association between ego dissolution and decreased functional connectivity between medial temporal lobe and high-level cortical regions. Ego dissolution also associated with "disintegration" of the salience network and reduced interhemispheric communication Completed Lebedev et al., 2015
Psilocybin Healthy volunteers 2 mg by i.v. infusion, once Increased between-network resting-state functional connectivity Completed Roseman et al., 2014
Psilocybin Healthy volunteers 30 mg/70 kg, once Psilocybin increases measures of mystical experience. Psilocybin experience has substantial personal meaning and spiritual significance. Sustained positive changes in attitudes and behavior attributed to the experience. Around 60% of participants rate their psilocybin experience among the most significant and spiritual in their lives Completed ClinicalTrials.gov identifier: NCT00802282 (Griffiths et al., 2006, 2008)
Psilocybin Healthy volunteers 10–20–30 mg/70 kg (low, moderate, and high dose, respectively) Dose-dependent effects of psilocybin on psychomotor performance, working memory, episodic memory, associative learning, and visual perception. No delirium or global cognitive impairment observed Completed ClinicalTrials.gov identifier: NCT02033707 Barrett et al., 2018
Psilocybin Healthy volunteers 15–20–30 mg, orally, once Compare altered states of consciousness induced by psilocybin, LSD, and mescaline Recruiting ClinicalTrials.gov identifier: NCT03604744, NCT04227756
Psilocybin Healthy volunteers 25 mg, orally, once Effects of SERT inhibition (escitalopram) on the subjective response to psilocybin in healthy subjects Recruiting ClinicalTrials.gov identifier: NCT03912974
Psilocybin Healthy volunteers N/A Application of PCI based on IIT. Combination of transcranial magnetic stimulation and high-density electroencephalography to measure electrocortical responses as distributed cerebral interactions (integration) and spatiotemporal pattern (information) Recruiting ClinicalTrials.gov identifier: NCT03853577
Psilocybin Healthy volunteers 0.2–0.215–0.315 mg/kg, orally, once Neuropharmacological mechanisms underlying ego dissolution. Integration of functional connectivity in sensory regions and disintegration in associative regions may underlie the psychedelic state Active, not recruiting ClinicalTrials.gov identifier: NCT03736980 (Preller et al., 2020)
AD, Alzheimer's disease; AIDS, acquired immunodeficiency syndrome; AN, anorexia BOLD, blood oxygen level–dependent; EEG, electroencephalogram; fMRI, functional magnetic resonance imaging; IIT, integrated information theory; MCI, mild cognitive impairment; NCT, ClinicalTrials.gov identifier; N/A, not available; OUD, opioid use disorder; PCI, perturbational complexity index; TPN, task-positive network; TRD, treatment-resistant depression.
Clinical trials available on ClinicalTrials.gov investigating the use of LSD as a potential therapeutic approach for MDD, anxiety, and other psychiatric disorders
Compound Cohort Regimen Research Question/Main Findings Status Reference
LSD Major depressive disorder First session: 25 or 100 μg, orally; second session: 25, 100, or 200 μg, orally Assess the benefits of LSD-assisted psychotherapy in patients with MDD Recruiting ClinicalTrials.gov identifier: NCT03866252
LSD Major depressive disorder First session: 25 or 100 μg, orally; second session: 25, 100, or 200 μg, orally Assess antidepressant and anxiolytic effects of LSD in patients with MDD Recruiting ClinicalTrials.gov identifier: NCT03866252
LSD Illness-related anxiety 20 or 200 μg, orally, once LSD reduces anxiety. Sustained anxiolytic effects and increased quality of life over a 12-mo period. Facilitated access to emotions and confrontation with previously unknown anxieties. The experience leads to a restructuring of the person's emotional trust, situational understanding, habits, and world view. No adverse reactions. LSD can be safe and generate lasting benefits in patients with a life-threatening disease Completed ClinicalTrials.gov identifier: NCT00920387 (Gasser et al., 2014, 2015)
LSD Healthy volunteers 100–200 µg, orally, once LSD induces visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Increased subjective well-being, happiness, closeness to others, and openness. LSD breaks down hippocampal-prefrontal cortex–mediated inhibitory processing, which might be involved in the formation of LSD-induced visual imageries. LSD increases blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. No severe acute adverse effects. LSD detected in all subjects up to 12 h after administration. Maximal LSD plasma concentrations reached 0.5–4 h after administration. Half-life of 2.5–4.5 h up to 12 h and slower elimination after. No sex differences in pharmacokinetics. Acute effects up to 12 h. LSD induces fewer mystical experiences than psilocybin. LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 µg compared with 100 µg. Feelings of ego dissolution at 100 µg correlated to LSD plasma levels Completed ClinicalTrials.gov identifier: NCT01878942 (Dolder et al., 2015; Schmid et al., 2015a; Strajhar et al., 2016)
LSD Healthy volunteers 100–200 µg, orally, once LSD impairs fear recognition and enhances emotional empathy and sociality. Maximum mean plasma concentration of 1.3 and 3.1 ng/ml reached 1.4 and 1.5 h after administration of 100 and 200 µg LSD, respectively. Mean plasma half-life 2.6 h. Subjective effects last 8.2 ± 2.1 h for the 100-µg and 11.6 ± 1.7 h for the 200-µg dose, respectively. Subjective peak effects reached 2.8 and 2.5 h after administration of LSD 100 and 200 µg, respectively. LSD reduces left amygdala and right medial prefrontal cortex activity during the presentation of fearful faces. Negative correlation between LSD-induced amygdala response to fearful stimuli and LSD-induced subjective drug effects Completed ClinicalTrials.gov identifier: NCT02308969 (Dolder et al., 2016, 2017b; Liechti et al., 2017; Mueller et al., 2017)
LSD Healthy volunteers 100 µg, orally, once Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to 5-HT2A. LSD impairs working memory, executive functions, and cognitive flexibility but not risk-based decision-making. 5-HT2A signaling underlies LSD-induced alteration of the neural response to dynamic changes in music. LSD decreases striatothalamic functional connectivity independently of 5-HT2A and increases thalamo-PCC connectivity in a 5-HT2A–dependent fashion Completed ClinicalTrials.gov identifier: NCT02451072 (Preller et al., 2018, 2019; Holze et al., 2019; Pokorny et al., 2019)
LSD Healthy volunteers 100 µg, orally, once LSD compared with MDMA produces greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity. LSD produces greater impairments in concentration, sense of time, and speed of thinking. LSD does not increase oxytocin levels. Acute LSD does not affect circulating BDNF Completed ClinicalTrials.gov identifier: NCT03019822 (Holze et al., 2020)
LSD Healthy volunteers 75 µg by i.v. injection, once LSD enhances suggestibility, and this effect could be harnessed in psychotherapeutic settings Completed Carhart-Harris et al., 2015
LSD Healthy volunteers 75 µg by i.v. injection, once LSD administration modulates learning adaptive mechanisms and attenuates top-down suppression of prediction error Completed Timmermann et al., 2018
LSD Healthy volunteers 40–80 µg by i.v. injection, once LSD enhances the emotional response to music. Increased functional connectivity between parahippocampal-visual cortex and increased parahippocampal-visual cortex information flow in the interaction between music and LSD Completed Kaelen et al., 2015
LSD Healthy volunteers 75 µg by i.v. injection, once LSD increases blood flow to the visual cortex and decreases alpha power, and these effects predict the magnitude of visual hallucinations. LSD decreases DMN integrity and delta and alpha power in the PCC, and these effects correlate with ego dissolution Completed Carhart-Harris et al., 2016c
LSD Healthy volunteers 75 µg by i.v. injection, once LSD increases brain entropy. Entropy increases are greatest while listening to music and experiencing ego dissolution Completed Lebedev et al., 2016
LSD Healthy volunteers 25–50–100–200 µg, orally, once per dose 5-HT2A receptor involvement in LSD consciousness-altering effects (using the 5-HT2A antagonist ketanserin before LSD) Completed ClinicalTrials.gov identifier: NCT03321136
LSD Healthy volunteers 100–200 µg, orally, once per dose Compare the acute effects of LSD and psilocybin Recruiting ClinicalTrials.gov identifier: NCT03604744
LSD Healthy volunteers 6.5–13–26 µg, orally, once per dose LSD microdosing produces dose-related subjective effects across the three doses. Microdoses increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content at 26 µg. Other mood, cognition, and physiological measures were unaffected. Low-dose LSD (13 µg) increases amygdala connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum and decreases amygdala connectivity with the superior temporal gyrus. Effects on mood positively correlated with the increase in amygdala-middle frontal gyrus connectivity Recruiting ClinicalTrials.gov identifier: NCT03790358 (Bershad et al., 2019, 2020)
LSD Healthy volunteers 13 µg, orally, once Assess the effects of repeated very low doses of LSD on mood in individuals with negative mood Recruiting ClinicalTrials.gov identifier: NCT03934710
LSD Healthy volunteers 100 µg, orally, once Comparative acute effects of LSD, psilocybin, and mescaline (Five Dimensions of Altered States of Consciousness and resting state fMRI) Not yet recruiting ClinicalTrials.gov identifier: NCT04227756
NCT, ClinicalTrials.gov identifier.
Clinical trials available on ClinicalTrials.gov investigating the use of ayahuasca and DMT for treatment-resistant depression and in healthy individuals
Ayahuasca Treatment-resistant depression 2.2 ml/kg, orally, once. Composition: 0.8 mg/ml DMT, 0.21 mg/ml harmine. No harmaline at detection threshold of 0.02 mg/ml (Osório et al., 2015; Sanches et al., 2016) 1 ml/kg, orally, once. Composition: 0.36 mg/ml DMT, 1.86 mg/ml harmine, 0.24 mg/ml harmaline, 1.20 mg/ml tetrahydroharmine (Galvao et al., 2018; de Almeida et al., 2019; Palhano-Fontes et al., 2019; Zeifman et al., 2019; Pasquini et al., 2020) Ayahuasca is a safe and well tolerated approach for TRD. Decreases in up to 80% of patients in depression-related scales from 80 min to day 21. Increased blood perfusion in the left nucleus accumbens, right insula, and left subgenual area. Vomiting in 47% of participants. Ayahuasca elicits fast-acting and sustained antidepressant effects. Ayahuasca decreases suicidality scores and might be useful for suicidality. Increased BDNF levels in patients with TRD and healthy controls 48 h after administration. Ayahuasca acutely increases salivary cortisol but does not affect awakening salivary cortisol response at 48 h in patients with TRD. At 24 h after ayahuasca, increased anterior cingulate cortex connectivity within the salience network, together with decreased PCC connectivity within the DMN, and increased connectivity between the salience and DMN. No effect on the connectivity of primary sensory networks Completed ClinicalTrials.gov Identifier: NCT02914769 (Osório et al., 2015; Sanches et al., 2016; Palhano-Fontes et al., 2019; Galvao et al., 2018; de Almeida et al., 2019; Zeifman et al., 2019; Pasquini et al., 2020)
DMT Healthy volunteers 15–25 mg by i.v. bolus + 0.6 to 1 mg/min by i.v. infusion over 90 min (total 69–115 mg) Psychological and physical tolerability of different intravenous DMT administration schedules to investigate the subjective and autonomic effects of prolonged DMT infusion in healthy subjects Not yet recruiting ClinicalTrials.gov Identifier: NCT04353024
NCT, ClinicalTrials.gov identifier; TRD, treatment-resistant depression.
Main receptor interactions and downstream effects of psychedelic compounds on pathways involved in synaptic and neuronal plasticity, neuroimmunomodulation, and modulation of neurotransmitter systems of relevance to psychiatry
For each compound (column 1), the receptors involved in signal transduction are reported with decreasing Ki (column 2). The transcription factors, enzymes, hormones, and cytokines up/downregulated by each compound are reported in terms of acute and chronic responses (where data are available, column 3). The main outcomes on modulation of neurotransmitter systems are reported in column 4. Systemic and psychological effects elicited are reported for each compound (column 5). Referenced articles are reported in column 6.
Receptors (>Ki)
Transcription Factors/Enzymes/Hormones/Cytokines
Neurotransmitter Effects
Central Effects/Systemic Effects/Psychological Effects
LSD 5-HT1B, 5-HT7, 5-HT6, 5-HT1A, 5-HT1D, 5-HT5A, 5-HT2A, D3, 5-HT2B, 5-HT2C, adrenoreceptor (ADRA) 2, 5-HT1E, D2, D4, D1, D5, ADRA1A, histamine receptor (H1), ADRB1, ADRB2, ADRA1B Acute: ↑mTOR, ↑cFOS, ↑Egr-1, ↑Egr-2, ↑Cebpb, ↑IKB, ↑SGK, ↑Nor1, ↑ANIA3, ↑MKP1, ↑DHEA, ↑CORT, ↓IL2, ↓IL4, ↓IL6, Chronic: ↑GABRB1, ↑GABRB2, ↑GABRG3, ↑NR2A, ↑NR2B, ↑BDNF, ↑KROX20, ↓D1, ↓D2, ↓5-HT2C, ↓SLC6A13 (GABA transporter) ↑(Prolonged) glutamate release in layer V pyramidal neurons, ↓5-HT firing in DRN via 5-HT2A (low doses), ↓DA firing via 5-HT1A (high doses), ↓DA neurotransmission in VTA (high doses) ↑Neurogenesis, ↑axon, branching, ↑synaptic scaling, ↓inflammation, ↓depression, ↓anxiety House et al., 1994; Watts et al., 1995; Egan et al., 1998; González-Maeso et al., 2003, 2007; Nichols and Sanders-Bush, 2004; Lambe and Aghajanian, 2006; Ray, 2010; Marona-Lewicka et al., 2011; Barrot, 2012; Martin et al., 2014; De Gregorio et al., 2016a,b; Ly et al., 2018; Rickli et al., 2015; Strajhar et al., 2016;
Psilocybin 5-HT2B, 5-HT1D, D1, 5-HT1E, 5-HT1A, 5-HT5A, 5-HT7, 5-HT6, D3, 5-HT2C, 5-HT1B, 5-HT2A, I1, SERT, ADRA2B, ADRA2A, ADRA2C ↑ACTH, ↑CORT, ↑TSH ↑Striatal DA release (caudate/putamen) ↑Neurogenesis, ↑axon branching, ↑synaptic scaling, ↓inflammation, ↓depression, ↓anxiety McKenna et al., 1990; Vollenweider et al., 1999b; Ray, 2010; Hasler et al., 2004; Carhart-Harris et al., 2016a
Ayahuasca 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5A, 5-HT6, 5-HT7R, TAAR1, S1R ↑5-HT2A, ↑SERT, ↑CORT (acute only), ↓CORT (awakening response), ↑GH ↑Hippocampal GABA (dose-independently); ↑amygdalar GABA (low doses); ↓amygdalar GABA (higher doses); ↑amygdalar 5-HT, DA, and noradrenaline; ↑hippocampal 5-HT (highest doses); ↑5-HT, DA, and noradrenaline turnover ↑Neurogenesis, ↑neuronal differentiation, ↓inflammation, ↓depression, ↓anxiety Callaway et al., 1999; de Castro-Neto et al., 2013; Morales-Garcia et al., 2017; Galvao et al., 2018; Palhano-Fontes et al., 2019
DMT 5-HT7, 5-HT1D, 5-HT2B, ADRA2B, ADRA2C, D1, 5-HT2C, 5-HT1E, 5-HT6, 5-HT5A, I1, ADRA1B, ADRA2A, ADRA1A, 5-HT2A, SERT, S1R ↑IL10, ↓IDO, ↓IL1β, ↓IL6, ↓IL8, ↓TNF-α N/A ↑Neurogenesis, ↑dendritic spines formation, ↓inflammation Fontanilla et al., 2009; Keiser et al., 2009; Ray, 2010; Tourino et al., 2013; Szabo et al., 2014;
5-MeO-DMT 5-HT1A, 5-HT7, 5-HT1D, 5-HT6, 5-HT1B, D1, 5-HT5A, 5-HT1E, D3, ADRA2C, 5-HT2C, ADRA2A, 5-HT2A, SERT, I1, ADRA2B, NET1, D4, D2, 5-HT2B ↑NMDAR, ↑ERK 1/2, ↑CREB, ↑CAMK2, ↓NF-ĸB, ↓NFAT, ↓TLR, ↓mGluR5, ↓PKC, ↓PLC, ↓IP3R, ↓EPAC1, ↓PKA, ↓IL1β, ↓IL6, ↓IL8, ↓TNF-α, ↑IL10 N/A ↑Neurogenesis, ↑dendritic spines formation, ↑long-term potentiation, ↓neurodegeneration, ↑cytoskeletal reorganization, ↓inflammation, ↑T lymphocytes differentiation, ↓cell death, ↓depression, ↓anxiety Ray, 2010; Szabo et al., 2014; Dakic et al., 2017; Lima da Cruz et al., 2018; Ly et al., 2018; Davis et al., 2019; Szabo et al., 2014
DOI 5-HT2C, ADRA2A, ADRB2, 5-HT2A, ADRA2B, 5-HT2BR, 5-HT1D, CHRM4, ADRB1, ADRA2C, SERT, 5-HT1E, CHRM3, H1, CHRM2, 5-HT6, CHRM5, 5-HT1A, CHRM1, 5-HT7, S1R, S2R, D1 ↑Egr-1, ↑Egr-2, ↑cFOS, ↑IKBA, ↓Egr-3, ↓TNF-α, ↓ILB, ↓IL6, ↓iNOS, ↓ICAM1, ↓VCAM1, ↓MCP1, ↓CX3CL1 N/A ↓Inflammation González-Maeso et al., 2003; Yu et al., 2008; Ray, 2010; Nau et al., 2013; Lima da Cruz et al., 2018
Ketamine NMDAR, D1, D2, 5-HT2A, 5-HT3, S1R, S2R, OPRM1, OPRK1, OPRD1 Acute: ↑mTOR, ↑BDNF, ↑IL1β, ↑IL6, ↑TNF-α, ↓EEAT2, Chronic: ↓TNF-α ↑DA activity via DR1 in the NA, ↑DA neurotransmission in VTA after amphetamine withdrawal ↑Neurogenesis, ↑dendritic spines growth, ↑synapse formation, ↑dopaminergic activity, ↓depression, ↓anxiety Li et al., 2010, 2017; Murrough et al., 2013b; Belujon and Grace, 2014; Belujon et al., 2016; Choi et al., 2017; Lisek et al., 2017;
MDMA TAAR1, NMDAR, VMAT2, 5-HT1A, SERT, I1, 5-HT2B, CACNA1A, ADRA2C, ADRA2B, CHRM3, ALPHA2A, CHRM5, CHRM4 ↑Cortisol, ↑prolactin, ↑oxytocin, ↑IL10, ↓IL1β, ↓IL6, ↓IL12, ↓IL15, ↓TNF-α, ↓CXCL10, ↓CCL5 ↑5-HT, DA, and NE neurotransmission; ↓5-HT and DA reuptake; oxytocin-dependent reopening of long-term depression in the NA ↓PTSD symptoms, ↑long-term depression in the NA, ↓inflammation Gouzoulis-Mayfrank et al., 1999; Ray, 2010; Boyle and Connor, 2010; Yuan et al., 2016; Mithoefer et al., 2018; Nardou et al., 2019
ADRA, alpha adrenergic receptor; ADRB, beta adrenergic receptor; ALPHA2A, alpha 2 adrenergic receptor; ANIA3, activity and neurotransmitter-induced early gene 3; CACNA1A, voltage-dependent P/Q-type calcium channel subunit alpha-1A; CAMK2, calcium/calmodulin-dependent protein kinase 2; CCL5, C-C motif chemokine 5; CHRM, muscarinic acetylcholine receptor M2; Cebpb, CCAAT/enhancer-binding protein beta; CORT, cortisol; CX3CL1, fractalkine; CXCL10, C-X-C motif chemokine 10; EEAT2, excitatory amino acid transporter 2; EPAC1, rap guanine nucleotide exchange factor 3; GABR, gamma-aminobutyric acid type B receptor; GH, growth hormone; I1, imidazoline receptor 1; ICAM, intercellular adhesion molecule; IP3R, inositol trisphosphate receptor; KROX20, early growth response protein 2; MAPK1, mitogen-activated protein kinase 1; N/A, not available; NET1, norepinephrine transporter 1; NFAT, nuclear factor o activated T-cells; NMDAR, N-methyl-D-aspartic acid receptor; Nor1, neuron-derived orphan receptor-1; OPRM1, mu-type opioid receptor; OPRK1, kappa-type opioid receptor; OPRD1, delta-type opioid receptor; IKB, inhibitor of kB kinases; PLC, pospholipase C; PKA, protein kinase A; PKC, protein kinase C; SGK, serine/threonine-protein kinase Sgk1; SLC6A13, sodium- and chloride-dependent GABA transporter 2; TLR, toll-like receptor; TSH, thyroid stimulating hormone; VCAM, vascular cell adhesion protein.
Data Supplement
Supplemental Table -
Supplemental Table 1 - Clinical trials available on ClinicalTrials.gov investigating the use of ketamine as a potential therapeutic approach for treatment-resistant depression and other psychiatric disorders.
Front Matter (PDF)
You are going to email the following Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Psychedelics in Psychiatry: Therapeutic Mechanisms
Pharmacological Reviews January 1, 2021, 73 (1) 202-277; DOI: https://doi.org/10.1124/pharmrev.120.000056
II. Psychedelic Compounds as Neuroplastic Agents
III. Psychedelic Compounds as Immunomodulatory and Anti-Inflammatory Agents
IV. Psychedelic Compounds as Modulators of Neurotransmitter Systems
V. Biased Signaling, Biased Phosphoproteomics, and Psychedelic Compounds
VI. Going Beyond Receptors: Neuronal Circuits Activated by Psychedelic Drugs
VII. Effects of Psychedelics on Sleep
VIII. Long-Term Neurobiological and Psychological Effects of Psychedelic Compounds
IX. Side Effects of Psychedelic Compounds
X. Recommendations for Future Research
XI. Conclusion
Authorship Contributions
Nanozymes for viral diagnosis and therapy
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Detective Alex Cross arrests renowned plastic surgeon Elijah Creem for sleeping with teenage girls. Now, his life ruined, Creem is out of jail, and he has made sure that no one will recognize him by giving himself a new face. A young woman is found hanging from a sixth floor window, and Alex is called to the scene. The victim recently gave birth, but the baby is nowhere to be found. Before Alex can begin searching for the missing newborn and killer, he is called to investigate a second crime. All of Washington, D.C. is in a panic, and when a third body is discovered, rumours of three serial killers send the city into an all out frenzy. Alex's investigations are going nowhere, and he is too focused on the cases to notice that someone has been watching him and will stop at nothing until he is dead.


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Singles Collection 1947-60
Genom Stan Freberg
Musikgenre Comedy
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Stan Freberg was a comedian, broadcaster, writer and actor who was best-known for his satirical radio shows and recordings during the 1950s and '60s. Starting his career providing the voices for cartoon animations at Warner Bros., he graduated in the late '40s to being a screen actor in satirical roles. He appeared on a 1947 release by Cliffie Stone's Barn Dance band before starting recording for Capitol under his own name in 1951, specialising in doing parodies of current popular songs and styles, and had nearly twenty charted hits during the '50s - quite a feat for comedy material which was out of the pop mainstream. This 45-track 2-CD set comprises the A & B sides of singles which were released during the period, and naturally features all his hits, including the No. 1 "St. George and The Dragonet", along with other Top 20 classics like "Little Blue Riding Hood" and the marvellous satirical takes on "The Yellow Rose Of Texas", "Sh-Boom", and "Cry". This was a fascinating and highly individual strand of the recording business of the era, when satirical comedy and social commentary of all kinds became popular during a time of social and musical upheaval, and this collection is an entertaining memento of one it's most distinctive practitioners
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Titel: Singles Collection 1947-60
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TheBridgeSchool.NET is pleased to announce their online summer school 2013 course offering.
Kids today have so much to juggle. They have to balance school, extracurricular activities, clubs, summer camps and jobs. Finding the time to excel at all of those things and maintain a social life is very challenging.
In addition, colleges and universities are raising their standards every year. Students have to find ways to stand out and differentiate themselves from the rest of the kids competing for acceptance.
Summer school is the perfect opportunity for students to get ahead…and even catch up.
"The Bridge School has a distinct advantage over other summer school programs in that we offer flexibility. We do not require students to come into a building during certain hours of the day and abide by a set schedule. Our courses are is available 24 hours a day, 7 days a week so students can log in when it fits their schedule. And our teachers make themselves available via email, text and Skype to answer questions and make sure their students are learning what they need to in order to earn course credit," says Scott.
The Bridge School also offers a secure Parent Portal so that parents and guardians can monitor their student's progress and grades in real-time.
"Since there is no minimum or maximum class size, students do not have to worry about registering for a course and then finding out later that it won't be offered. That doesn't happen because we are online and have more flexibility than a brick and mortar school that has to find classroom space and hire a teacher. The Internet is our classroom and we have certified teachers for all course areas," says Scott.
The Bridge School was a wonderful, very simple, easy experience for me, the instructor was very helpful. It made my experience that much more enjoyable.
My experience was pretty good overall – my teacher and mentor were both very helpful.
With more than 100 courses in the 2013 summer school session such as English, all Sciences, all Math courses, Social Studies & History, AP and Dual Credit and major Electives, The Bridge School is a great choice for students who require that flexibility in their schedule.


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JSHS Competitions Offer Big Scholarships for Student Researchers
Each fall, regional program directors for the Junior Science and Humanities Symposia (JSHS) put out calls for high school research papers. One of several prestigious national competitions, the JSHS offers unique opportunities for students to present original research to panels of expert judges and potentially win college scholarships amounting to thousands of dollars.
Unlike more familiar competitions sponsored by Intel and Siemens, JSHS departs from a traditional science fair format and employs a process more similar to that used for scientific or academic conferences and publications. Students are asked to submit abstracts for consideration at a regional level. If accepted, the research is then presented at a conference or symposium.
JSHS regional and national symposia are held during the academic year and typically reach over 12,000 high school students throughout the US, Puerto Rico, and the Department of Defense Schools of Europe and the Pacific Rim. Each of 48 university-held regional symposia invites participation from secondary schools within their region.
The DC area is covered by three separate regions and includes symposia held at James Madison University, Georgetown University, and Morgan State University. It's a complicated arrangement, but students have a fair amount of flexibility about where to submit abstracts and are not limited by residency.
Although the DC deadline for submission has passed for this year, Virginia and Maryland are still accepting abstracts. DC students in high schools not already participating at Georgetown may still be eligible for consideration by Virginia or Maryland.
The competition requires an original research project on a topic in one of six general categories including:
Environmental science including earth and space science
Physical sciences including chemistry, physics and astronomy
Medicine and health; behavioral and social sciences
Work may be part of a class project, a summer research project, or a science fair entry.
And the rewards are huge. Regional finalists receive scholarships, an expense-paid trip to the National JSHS, which is in San Diego this year, and an opportunity to compete for additional scholarships up to $12,000. Six big winners at the national event win expense-paid trips to the London International Youth Science Forum.
Originated in 1958 as part of a greater effort to focus attention on the sciences and scientific research, the Junior Science and Humanities Symposia Program is sponsored by the US Departments Army, Navy, and Air Force. In addition to the financial incentives, students who participate get to interact with practicing researchers and potentially have their work published.
For more information and participation guidelines, visit the JSHS website. Links to regional competitions and application materials may be found on the contacts page.
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Emma Bennett adjusts to life after losing her husband in a car accident. After a break-in of her home, where the only items stolen are her husband's hat and boots, she suspects a man from her past is stalking her again.
When Emma's daughter begins waking in the night, claiming to see her father outside her window, Emma begins to doubt her theory and wonders if death is as final as she'd always thought.


How do you accidently remember wrongly that you were in an aircraft that was shot down?
Williams has been telling a story about how he was in a helicopter forced down after taking an RPG hit in Iraq in 2003. It turns out that it's all completely true except for the part where he was in a helicopter forced down after taking an RPG hit in Iraq in 2003.
Murdoc thinks he know what caused this mistake, Brian. (May I call you Brian?) I think that the cause of the conflation was probably was most people call "lying." You were lying Brian. Lying.
Brian Williams of NBC News is a liar.
What affected Brian Williams' mind is the same thing that affected Hillary's mind when she remembers flying into Afghanistan and land following a corkscrew descent to the airport all the while receiving fire from the Taliban.
But I think that Murdoc has the right of it in both cases, liar, liar, pants on fire. A lie in both cases to give greater credibility to the liar.


text:
package io.squark.yggdrasil.jsx.cache;

import io.squark.yggdrasil.jsx.servlet.JsxRequestContext;

import java.io.Serializable;

public class CacheKey implements Serializable {
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        this.jsxRequestContext = jsxRequestContext;
    }

    public JsxRequestContext getJsxRequestContext() {
        return jsxRequestContext;
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    @Override
    public int hashCode() {
        return jsxRequestContext != null ? jsxRequestContext.hashCode() : 0;
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    @Override
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        if (o == null || getClass() != o.getClass()) return false;

        CacheKey cacheKey = (CacheKey) o;

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               cacheKey.jsxRequestContext == null;
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    @Override
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        return "CacheKey{" + "jsxRequestContext=" + jsxRequestContext + '}';
    }

}

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Within the healthcare industry, there is a great deal of discussion regarding the occurrence of a "patent cliff." In 2013, several brand name drugs' patents will expire which will result in the release of their generic equivalents to the market. Generic drugs are less expensive versions of brand name drugs that contain the same active ingredients as their branded counterparts offering equivalent usage, safety and efficacy at a typically lower cost. It has been noted that approximately 80% of a brand name drug's sales volume is replaced by its generic counterpart within six months of its patent expiration. As a result, pharmaceutical companies have applied the term "patent cliff" to the unusual large number of drugs going off patent in the next few years and the reduction of revenue they will experience due to the loss of major brand name drug patents.
As prices continue to rise in the area of pain management, it is important to look for cost savings, especially in the area of prescription medications. One such opportunity is when a brand medication goes off patent. When the generic formulation is approved to be released on the market, a cost savings can be realized anywhere from 20% to as much as 90% over time as competition between manufacturers supplying the generic increases.
We saw this in 2012 with the release of generic Kadian (Morphine Sulfate CER), with a reduction in cost from $9.73 per capsule for brand (Kadian CER 30mg) to $5.46 per capsule for the generic medication of the same dosage. The same was true for generic Lexapro 20mg (Escitalopram Oxalate) at a cost per tablet of $3.72 versus $5.46 for brand (Lexapro 20mg). In 2013, there are several frequently prescribed brand name drugs whose patents will expire. Of these drugs, the most highly utilized within the workers' compensation industry include Opana ER and Oxycontin (both are long acting opioid medications utilized for the treatment of chronic pain), Cymbalta (frequently prescribed for chronic musculoskeletal pain and depression) and topical Lidoderm patches (most often used off-label for treatment of neuropathic pain other than diabetic neuropathy). All were listed in the top 20 medications by spend and transactions in the PMSI 2012 Annual Drug Trends Report for Workers' Compensation.
Opana ER– In mid December 2012, the FDA approved the generic formulation of brand Opana ER (Oxymorphone Hydrochloride TER) to be released as well as approving the new tamper resistant product, which will not have a generic equivalent at this time. The first generic Opana ER products were released in early January 2013 with savings of almost a dollar per pill. Generic Oxymorphone HCL TER 15mg costs $5.17 per tablet versus $6.07 for brand Opana ER 15mg. For an injured worker taking 60 pills per month with a life expectancy of 25 years that amounts to a lifetime savings of $16,200.
Oxycontin– Purdue, the manufacturer of brand Oxycontin, has for years successfully blocked release of generic equivalent products through litigation. The patent for the original formulation of Oxycontin is set to expire on April 16, 2013.However, Purdue has begun studies to test Oxycontin's use for pain in children which could help them secure a six month extension for the drug's original patent. At this time the extension is still pending approval by the FDA. Purdue has also reformulated the original Oxycontin to create a more tamper resistant product and is arguing that the generic formulations should be required to adhere to the newer, more tamper resistant formulation guidelines to reduce their potential for abuse. If the FDA agrees, then the generic formulations could not be released until the patent for the new formulation of Oxycontin is set to expire in 2025. Oxycontin was listed as #1 and #3 in total spend and transactions respectively in the PMSI 2012 Drug Trends Report for workers' compensation. Therefore, the availability of a generic product would yield meaningful savings on claims where it is being prescribed.
Cymbalta– Cymbalta, whose patent was set to expire in June of 2013, was just awarded a patent extension of 6 months due to the FDA's pediatric-exclusivity program for its studies testing use of Cymbalta in children and adolescents. Therefore, it is difficult to predict exactly when this drug will come off patent.
Lidoderm patches-Watson Pharmaceuticals received final approval by the FDA for its generic version of Lidoderm and was given 180 days of marketing exclusivity pursuant to an agreement with the manufacturer of the brand name product on May 29, 2012. The generic product is set to be released in September of 2013 when brand Lidoderm's patent is set to expire. Even though topical Lidoderm patches are most often prescribed off-label to treat neuropathic pain in workers' compensation injuries and therefore does not impact MSAs, it does have an impact on the ever rising pharmacy costs of the claim itself. It was listed #2 behind Oxycontin in the top 20 medications of total spend in the PMSI 2012 Annual Drug Trends Report for Workers' Compensation.
As healthcare expenditures continue to climb within the workers' compensation industry, particularly in the area of prescription medications, generics can play a key role in helping to lower costs. It is important for the workers' compensation industry to stay abreast of patent expirations and leverage this information for overall claim savings as well as MSA savings. PMSI's PBM has numerous programs that have driven high levels of generic utilization for our clients. These programs have produced significant savings and helped clients lower both claims costs and MSA allocations.
Florida District Court Denies Request to Opine on the "Question that Confounds" Tort Litigation Parties: Do we need an LMSA?
The price of Lexapro has not dropped much as a generic. Not enough companies are getting on board to make it to produce real competition in prices – in particular, I don't think Ranbaxy is interested.


The BMW X5 is appealing to customers due to its sporty looks and nature. There are four models available – 2 rear wheel drive and 2 all-wheel drive. The X5 comes with seven seats which is what sets it apart from competition. The extra seat does eat into the boot space but nonetheless, its still pretty roomy. Comfort level on the second and third row can be questioned, also, the third row is suitable only for children or luggage. This big, powerful SUV is agile and responsive with emphasis on comfort, safety and luxury. The car proves an irresistible draw because of its cabin comfort, sporting performance and luxury. Best luxury SUV out there-BMW X5.


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http://www.smcm.edu/africandiaspora/
jlcoleman@smcm.edu
Organization Description
African and African Diaspora Studies is designed to help students explore, examine and critically analyze the African presence in a global context, stretching back to antiquity in Europe and Asia, and for centuries in the Americas.
Professor of English Jeffrey Coleman Published in Book on Black Intellectual Thought of the Twentieth Century
Jeffrey Lamar Coleman, professor of English, published "Singing Is Swinging: The Soul Force of Twentieth Century Black Protest Music" in "The Black Intellectual Tradition: African American Thought in the Twentieth Century" (University of Illinois Press, 2021). The book presents essays on the… Find Out More
St. Mary's College to Host "From Invisibility to Remembrance" Symposium
The African and African Diaspora Studies program at St. Mary's College of Maryland will host its second annual fall symposium, "From Invisibility to Remembrance: Commemorating Slavery at St. Mary's and Beyond," on Wednesday, Oct. 2 beginning at 8 p.m. in Cole Cinema, Campus Center, and on Thursday… Find Out More
Dr. Yasser Elshayeb to Discuss ScanPyramid Mission, Discovery
St. Mary's College of Maryland welcomes Dr. Yasser Elshayeb from Cairo University to campus to discuss a recent discovery at the great pyramids on Friday, Sept. 28 at 4 p.m. in Cole Cinema located in Campus Center. This event is free and open to the public.
Elshayeb is the deputy coordinator of… Find Out More
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Seamless tubes - solid posts.
Heavy-duty bars. Available new lock operates from top, no more inadvertent unlocking to scratch desk.
In production for nearly 60 years.
Covers available in library grade Buckram, Poly and Expanded Vinyl.


text:
Q: Eclipse 4.7.2 not showing projects after sudden computer restart I was working in eclipse, on a 100% working workspace, when suddenly my computer froze. I couldn't kill the broken processes so I had to shutdown the system using my computer power button (eclipse was open the whole time). After the system startup I opened eclipse and... the workspace loads, the theme, code formatting, etc. is there, but all the projects are gone. They are still present on the disk, at the same spot, the workspace just stopped showing them...
I know, I can import the existing projects into workspace and that would fix it, but it would also break the working sets and some other stuff, so... Is there any way in which I could repair the workspace?
Logs from my workspace .metadata folder: .log
My eclipse version: About Eclipse

A: After some testing using an old (almost 3 months old) backup I found out that the file in which eclipse stores workspace file tree is almost empty. But in my backup - it is almost 300 KB. So I came up with three solutions:

*

*Just re-import everything to the workspace

*Take the .history, .root and .safetable folders from a backup and paste the into .metadata.plugins\org.eclipse.core.resources folder (some projects might be missing and working sets might still be empty)

*Just backup your workspace daily, like I should have done and your loss will be minimal

redpajama_set_name: RedPajamaStackExchange


December 28, 2010 • Until the 1980s, thousands of rebellious Swiss youths were locked up without trial. Officials called it "administrative detention." But in reality, the kids were put in prison or labor camps. Now, many victims are demanding accountability and compensation for damaged lives.
December 24, 2010 • Germany's government has announced plans to scrap compulsory military service and optional community service. That's left many social service agencies deeply worried. They rely on the 90,000 conscripts who opt for the alternative community service.
December 18, 2010 • Fed up with shockingly low pay and long hours, doctors in the Czech Republic are threatening to leave the country en masse. It's made no difference yet to the cash-starved government, which is moving ahead with cost-cutting plans.
December 16, 2010 • European leaders are gathering in Belgium to look for ways to end the continent's debt crisis. Greece and Ireland both needed bailouts this year, and there are fears that the crisis could spread. Despite frequent calls for coordinated action, officials are divided on how to solve the problem.


Two friends win a journey on a cruise ship with their favorite TV-show-master. When he surprisingly dies they try to cover up his death to find the murderer.
The second movie by the two Bavarian comedians, Erkan and Stefan. They discover an ancient dagger and free the beautiful warrior virgin Tana (Bettina Zimmermann) from it. Evil sorcerer Kartan, however, wants both the dagger and the virgin for a sacrifice ceremony. Erkan and Stefan rely on their video game experience to defeat the dark forces. At a length of only 77 minutes, the movie doesn't slow down too often between the gags, so if you have got the appropriate sense of humor, you may find this quite enjoyable. Excellent: Corinna Harfouch as the teacher who breaks her own rules to solve problems without violence. On the other hand, the performance of Bettina Zimmermann is disappointing. One needs more than wildly rolling eyes to follow the footsteps of a Michelle Yeoh or Sandahl Bergman. The parody elements are reminding me of movies like Stephen Sommers' "The Mummy", Harold Ramis' "Bedazzled" and J. Lee Thompson's "Firewalker", among others.


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Matapouri () is a coastal settlement in the Whangarei District of Northland, New Zealand. It is 7 km north of Tutukaka and 35 km north-east of Whangarei, in an area known as the Tutukaka Coast. Matapouri was described by Whangarei District Council in 2010 as "an archetypal Kiwi bach settlement". Holiday homes make up 90 per cent of the houses and at holiday times the number of residents swells to seven times its permanent population.

History
The early European settlement of Matapouri was based on the milling and transport of timber. The first school was built in 1899 and the first recorded store in 1912.

Te Wai o Te Taniwha, the Mermaid Pools, was an informal tourist attraction, but was closed indefinitely in 2019 by the local Māori authorities, Te Whanau ā Rangiwhakaahu Hapū Trust, due to visitors leaving toilet waste and rubbish.

Demographics
Statistics New Zealand describes Matapouri as a rural settlement. The settlement covers . The settlement is part of the larger Matapouri-Tutukaka statistical area.

Matapouri had a population of 192 at the 2018 New Zealand census, an increase of 45 people (30.6%) since the 2013 census, and an increase of 48 people (33.3%) since the 2006 census. There were 69 households, comprising 90 males and 99 females, giving a sex ratio of 0.91 males per female. The median age was 46.1 years (compared with 37.4 years nationally), with 42 people (21.9%) aged under 15 years, 21 (10.9%) aged 15 to 29, 96 (50.0%) aged 30 to 64, and 33 (17.2%) aged 65 or older.

Ethnicities were 65.6% European/Pākehā, 37.5% Māori, 10.9% Pacific peoples, 4.7% Asian, and 1.6% other ethnicities. People may identify with more than one ethnicity.

Although some people chose not to answer the census's question about religious affiliation, 42.2% had no religion, 45.3% were Christian and 4.7% had other religions.

Of those at least 15 years old, 36 (24.0%) people had a bachelor's or higher degree, and 18 (12.0%) people had no formal qualifications. The median income was $27,400, compared with $31,800 nationally. 24 people (16.0%) earned over $70,000 compared to 17.2% nationally. The employment status of those at least 15 was that 63 (42.0%) people were employed full-time, 21 (14.0%) were part-time, and 12 (8.0%) were unemployed.

Matapouri-Tutukaka statistical area
Matapouri-Tutukaka covers  and had an estimated population of  as of  with a population density of  people per km2.

Matapouri-Tutukaka had a population of 1,692 at the 2018 New Zealand census, an increase of 345 people (25.6%) since the 2013 census, and an increase of 489 people (40.6%) since the 2006 census. There were 657 households, comprising 846 males and 846 females, giving a sex ratio of 1.0 males per female. The median age was 49.1 years (compared with 37.4 years nationally), with 297 people (17.6%) aged under 15 years, 198 (11.7%) aged 15 to 29, 834 (49.3%) aged 30 to 64, and 363 (21.5%) aged 65 or older.

Ethnicities were 89.4% European/Pākehā, 17.7% Māori, 2.5% Pacific peoples, 1.8% Asian, and 2.1% other ethnicities. People may identify with more than one ethnicity.

The percentage of people born overseas was 22.0, compared with 27.1% nationally.

Although some people chose not to answer the census's question about religious affiliation, 64.0% had no religion, 26.6% were Christian, 0.4% were Hindu, 0.2% were Muslim, 0.2% were Buddhist and 2.7% had other religions.

Of those at least 15 years old, 384 (27.5%) people had a bachelor's or higher degree, and 159 (11.4%) people had no formal qualifications. The median income was $32,300, compared with $31,800 nationally. 258 people (18.5%) earned over $70,000 compared to 17.2% nationally. The employment status of those at least 15 was that 630 (45.2%) people were employed full-time, 249 (17.8%) were part-time, and 36 (2.6%) were unemployed.

Amenities
Matapōuri Marae is a meeting ground for Ngāti Rehua, Ngāti Toki-ki-te-Moananui of Ngātiwai, and Te Whānau a Rangiwhaakahu of Te Āki Tai. It includes Te Tokomanawa o te Aroha meeting house.

The present Matapouri Hall, based on a Keith Hay Homes design, was constructed on site in the 1970s. The hall has hosted organisations such as the Women's Institute as well as providing a place for church services, polling booths, social gatherings, New Years gala and other community events throughout the years. An earlier hall built in 1912 was demolished in 1970.

References
Citations

Works cited

Whangarei District
Populated places in the Northland Region

redpajama_set_name: RedPajamaWikipedia


Scapa Flow is consolidating its position as the European centre for excellence for ship-to-ship (STS) operations at anchor of crude oil and other products, with a particularly busy period for the harbour about to get underway.
The harbour authority, OIC Marine Services, is over the next week preparing for the arrival of over 15 Aframax, Suezmax and VLCC tanker types to undertake eight STS operations.
In addition to that activity, the departure of the drilling rig Stena Don, and Prosafe accommodation vessel Safe Caledonia is also imminent, with both companies planning to return to Scapa Flow later this year.
Talking about the Scapa Flow Oil Port activity, Orkney Islands Council business development manager Michael Morrison said: "The experience and knowledge that the pilots, pilot boat crews, tug crews and operational staff, led by the harbourmaster have acquired through carrying out multiple STS operations over many years is unrivalled, resulting in giving Scapa Flow the industry recognition it deserves for these seamless operations."
He said that this had led to Scapa Flow being recognised as a European centre for excellence for such operations within the industry.
As well as the upturn in oil port activity, cruise season is also well underway, with the second visit of the largest cruise ship of the year, MSC Meraviglia, which is due on Tuesday at Hatston Pier.
The prestigious Cunard liner Queen Victoria is also due in Kirkwall tomorrow, Friday.


There's a real need for small business to add at least some social media as one of the arrows in their marketing quiver. That said, here's a couple of social media tips for small business owners that will help you to achieve the most from this Internet advertising tool.
You'll need to understand the differences between Twitter, Facebook or any of the other vehicles you choose and more traditional ways of advertising. Rule number one and perhaps the most important of the social media tips for small business owners presented here has to do with tone.
In short, gone are the days of the hard sell, hard hitting, right-between-the-eyes ad copy that told you in no uncertain terms what it wanted you to buy and when. Social media is much more personal and your posts should reflect a more conversational style and intimate approach. Prospects relate more to who you are on Twitter than what you've got to sell. Positioning yourself with kindly insider information convinces readers you're an expert they should be buying from.
Persistence is another virtue. Get into the routine of checking to see if people have been reading your posts and respond accordingly. Setting aside the same block of time each day helps to groove this practice so it becomes a routine.
Starting any campaign with a few social media tips for small business owners takes a lot of the guesswork out of getting the best from any of these platforms.
This entry was posted in Online Marketing and tagged on February 11, 2013 by ReferLinks Online Marketing.


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Phoenix, America's inflation capital, seeing record lines at food banks as desperate locals struggle to eat
The worst place in the country to live right now in terms of inflation is Phoenix, where reports indicate a record number of struggling locals are lining up at food banks just to eat.
The latest figures show that Phoenix is still the hardest-hit city with a 12.1 percent inflation rate. As a result, St. Mary's Food Bank, as one example, is seeing a daily lineup of hundreds of cars in three lanes around its local warehouse. In an average week, some 1,000 cars pass through the facility for food.
"Every time we thought we hit a peak, it continued to grow and here we are, in December," said Ken Pertis, president of what is the world's first food bank. "Across our whole network, we've seen a 26 percent increase in the number of people coming to us right, year over year."
Right now, Phoenix residents are having to shell out about 21.1 percent more for food and other goods compared to what they were paying at the end of 2020. This averages out to about $912 in additional spending per month for area residents.
One local named Desirea Lopez, 36, started getting food support at St. Mary's after her family's home rent increased another $25 to $1,450 per month. Turning down the lights and energy usage coupled with relying on St. Mary's for a little extra help is keeping Lopez's family fed.
"It's very important coming here because sometimes if I don't get the chance to come, then we start missing out on the meal," she said. "I won't eat. She'll eat first." (Related: Everything seems to be converging towards a global calamity, the likes of which has never before occurred in human history.)
Will inflation subside or get worse in 2023?
The price of gas is also hitting families hard, though one bit of good news is that gas prices have subsided some since their all-time highs earlier this year. It remains to be seen what happens with gas and other prices in 2023.
The lines for food in the lead-up to Christmas at St. Mary's were not quite as hectic as the week before Thanksgiving when people were coming there in search of turkeys for their families, according to Pertis.
"It was probably three, four miles each way," he said about the Thanksgiving lines.
Many of the people who showed up for that holiday were first-time visitors who had never before used a food bank. This speaks volumes as to the dire state of the economy when people who were previously living just fine are suddenly finding themselves in poverty.
"They're not here because they want to be here but because they have nowhere else to turn," Pertis said. "It's the impact of the economic insecurity caused by inflation."
One of the reasons why Phoenix's inflation rate is substantially higher than that of the rest of the country has to do with its real estate market, according to Pertis.
"After COVID, we had the federal government putting money into the economy with stimulus packages and we had the Federal Reserve making borrowing almost nothing," he explained.
"That allowed a lot of investors to either move up in their homes or buy additional homes. Now that impact was more pronounced in the high growth areas that typically do well for investors."
Pertis also blamed lots of people moving to Arizona from other states, especially during COVID. He told the media that it helped drive up demand and thus prices.
"When they come here, the prices go up for everything," he stated.
More of this type of news can be found at Collapse.news.
Tagged Under: America, cancel Democrats, Collapse, currency crash, dollar demise, food banks, food prices, gas prices, homelessness, hunger, Inflation, liberal policies, pensions, phoenix, Real Estate, risk, starvation
Richard Proctor: International banking establishment is controlling people's lives through money manipulation
GOP lawmaker introduces 'Fair Tax' legislation that would neuter IRS and greatly simplify the tax code
Controlled demolition of global finance system sees failing cryptos, bank runs and soon, the unveiling of Central Bank Digital Currencies (CBDC)
Biden's economy: After two years of Democratic economic policies, major companies continue to shed employees
Economists predict US economy to enter RECESSION in 2023
Supreme Court to hear two challenges against Biden's student loan debt forgiveness plan
Covid tyranny is about money and keeping the corrupt global financial system intact – not public health
Only 20% of rail services are running normally in the UK as rail strikes cause widespread disruptions
Most major banks agree: 2023 spells BIG TROUBLE for the U.S. economy
Democrat-induced food inflation set to continue into 2023, offering hard-pressed American families no relief
To prevent bank-run panic, the FDIC is conspiring to blind Americans to the impending market collapse
Biden's economy has produced the worst home market since World War II as values continue to decline
Cryptocurrency firm Midas Investments closes platform following losses in wake of FTX collapse
Economists: Over $31 trillion national debt could lead to slow-moving economic demise
Outrageous! Biden, Congress send billions to Ukraine but fail to pay National Guard troops on time
15 Facts which prove that a massive economic meltdown is already happening right now
Gregory Mannarino: Central banks are about to issue even more debt to make society more dependent on them
It's only money: Congress set to pass ANOTHER massive $1.7T spending bill, thousands of pages long, without reading it
CFPB orders Wells Fargo to pay $3.7 billion for gross mismanagement of auto loans, mortgages and deposit accounts


In psychology, an attribution bias or attributional bias is a cognitive bias that refers to the systematic errors made when people evaluate and/or try to find reasons for their own and others' behaviors. People constantly make attributions regarding the cause of their own and others' behaviors; however, attributions do not always accurately mirror reality. Rather than operating as objective perceivers, people are prone to perceptual errors that lead to biased interpretations of their social world.
Attribution biases are present in everyday life, and therefore are an important and relevant topic to study. For example, when a driver cuts us off, we are more likely to attribute blame to the reckless driver (e.g., "What a jerk!"), rather than situational circumstances (e.g., "Maybe they were in a rush and didn't notice me"). Additionally, there are many different types of attribution biases, such as the fundamental attribution error, actor-observer bias, and hostile attribution bias. Each of these biases describes a specific tendency that people exhibit when reasoning about the cause of different behaviors.


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Dedicated volunteer picks up prestigious award
Cole double secures 5th straight win
Fresh appeal launched for wanted man
Fundraiser launched to help pensioner
27/11/20 • By Jack Tolson
A FRIEND of an elderly man who was robbed of £20,000 in a 'terrifying' raid has set up a fundraiser to try and claw some of the money back.
Malcolm Hodgson, 74, was robbed by two conmen, James Hughes, 37 of no fixed abode, and Wayne Roberts, 36, formerly of Burton Road, after they let themselves into his Mapplewell home and lied about their reasons for being there, before punching the victim in the face.
The pair had managed to steal £20,000 from the elderly man after keeping him captive for around an hour while they robbed him, threatening violence and injury if they did not comply with their demands.
Roberts was found guilty of robbery following a jury trial and jailed for 14 years, whilst Hughes, who had pleaded guilty to robbery before the trial as well as an additional count of burglary relating to a separate incident, received a four-year sentence.
In a bid to help support Mal one of his friends, 28-year-old Laura Yoxall of Stairfoot, set up a fundraiser to try and collect £1,000 for the man - more than £600 has already been raised.
She said: "I've set the fundraiser up to try get him a little bit of his money back as they never recovered the money.
"I know I'll never get the £20,000 back but I'm just happy reaching the target of £1,000.
"I will be putting the money straight into Mal's bank account and then I'll leave it running for around a month or so.
"I'm currently doing football scratch cards to raise funds which is going really well - my brother Luke is also doing them."
To donate to Laura's fundraiser, visit gofundme.com/f/m8mj2b-help-mal-get-back-on-his-feet.
Duff rues 'harsh' red but admits team 'not at races'
Defibs installed at every station
Reds 'outfought and outrun' in 'unacceptable' cup loss
Talking points from Derby loss
Cundy and Benson out, Thomas and Tedic closer
Town centre venue subject to 'police witch hunt'
A third of 999 calls dealt with within 15 minutes
Williams would welcome competition at right wing-back
Miners' lives remembered at annual memorial event
£2m active travel hub approved
MP: Veterans' accommodation needs to be improved


Microsoft Office's outdated licensing requirements raise the cost of Microsoft Dynamics ERP in the cloud, costing Dynamics customers thousands in unnecessary Office license fees.
It is no secret that Microsoft Dynamics has worked hard in the last few years to become the go-to solution for cloud based business management and enterprise resource planning (ERP). Dynamics hosting providers are now able to offer the power of choice to their customers through a variety of Cloud options. The Microsoft Dynamics ERP Services Provider Licensing Agreement (SPLA) is the main driver behind Dynamics hosting licenses, giving customers the option to pay for their software licenses on a monthly basis to reduce their upfront ERP licensing costs and capital expenditures. However, the Microsoft Office side is making it difficult for Dynamics hosting partners to deliver the full value of the cloud to their customers due to outdated licensing requirements for Office products.
One of the greatest benefits to Dynamics customers is the integration and interoperability between Dynamics ERP and the Microsoft Office suite. Excel reports can be seamlessly and easily exported to and from Dynamics ERP products, as well as data from Word-based templates for billing and invoicing. Since most businesses are already running Office, this is a huge benefit for them. Unfortunately the pre-cloud, pre-mobile thinking behind Microsoft Office licensing often requires Dynamics Hosting customers under SPLA to purchase duplicate Office licenses for each user in order for Office to work with the hosted Dynamics solution. This leads to unnecessary costs to the customer that can reach into the tens of thousands depending on the number of users.
Under the Microsoft Office licensing rules, SLPA Dynamics customers in a shared hosting environment are not allowed to use their existing Office license to access Office software through Dynamics when it is deployed over a remote desktop connection. This includes Azure and hosting partners' cloud environments. In order for a customer to use their existing licenses with hosted Dynamics, Office licensing rules currently require the server to be dedicated to that customer. But to do this would undermine much the benefits from deploying cloud based Dynamics through a hosting provider and essentially forces hosting customers to purchase the duplicate licenses regardless.
Customers are required to purchase additional licenses whether they deploy Office locally or through the cloud via Office 365 (O365).
The simple solution would be to grant Mobility Rights to Office volume licenses under SPLA. Mobility rights give the licensee freedom to deploy Office on a number of devices and should therefore allow the customer to purchase Office and let the hosting provider deploy it in the provider's shared hosting environment. However, the Microsoft Office team has shown no indication that they intend to offer this as a solution anytime in the near future.
Despite the unnecessary licensing fees for Office and O365, deploying Microsoft Dynamics ERP in the Cloud via a hosting a provider's shared environment still creates significant cost savings over on-premises deployment. This allows small and mid-size organizations to leverage a solution that they would otherwise not have the resources to deploy in house. It also allows large-scale enterprise Dynamics customers to deploy a cloud or hybrid solution to gain the power of cloud choice with anytime anywhere access.
Microsoft Dynamics Web Client users are not subject to the additional fees as they access their Dynamics solution using a web browser. However, not all of the ERP products have complete functionality available in the Web Client. And further, not all Independent Software Vendors (ISV) solutions have ported their applications to work with the newly released web client, so therefore this is not always an option for a customer.
Microsoft Dynamics is still the best ERP cloud choice for businesses that use Office to run daily operations. But Dynamics hosting providers like RoseASP who are dedicated to delivering the greatest value in products and services to their customers face a major challenge to delivering value with the Office licensing restrictions, and customers suffer unnecessary fees in a time when everybody is pinching every penny.


To offer continuing education for professionals, HEC Montréal is setting up a new pavilion in the downtown core, bringing it closer to the business community. Trizart Alliance is designing multimedia systems for more than 30 teaching spaces with a capacity ranging from 30 to 220 places, 25 meeting rooms and 55 team work spaces that will be located on the 8 floors of the new building.
Copyright © 2015 Trizart Alliance. All rights reserved.
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By former Ailey company member Marcus Jarrell Willis, gives physical life to our inner thoughts. Willis weaves six simple gestures into "the stream," the tumultuous monologue within each person's mind. Set to a contemporary reimagining of Vivaldi's Four Seasons by Max Richter, this work echoes the tension and poignancy of the music's ever-changing tides.
Princess Grace Award-winning choreographer Jae Man Joo's Circular is a heartfelt conversation through movement. The Korean-born Joo's distinctive choreographic style – a blend of classical and contemporary ballet – is showcased in this large ensemble work that captures the full circle of human emotions. The melodic soundscape is by a diverse group of composers, including Denisov and Handel.
In Sketches of Flames, Bridget L. Moore fuses flamenco influences with her African-American and contemporary aesthetic to create a rapturous ensemble dance. Set to a series of passionate folk songs and drawing upon the writings of Federico García Lorca and others, each section of this eight-part work depicts a different facet of the joys and sorrows of love.