***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objectives : The objective of this prospect i ve , open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in participants with treatment-resistant chronic pain . Patients and Methods : The primary outcome was the change in the pain symptom score on the S-TOPS ( Treatment Outcomes in Pain Survey — Short Form ) question naire at the 6-month follow-up in an intent-to-treat population . Secondary outcomes included the change in S-TOPS physical , social , and emotional disability scales , the pain severity , and pain interference on the Brief Pain Inventory , sleep problems , and the change in opioid consumption . Results : A total of 274 participants were approved for treatment ; complete baseline data were available for 206 ( intent-to-treat ) , and complete follow-up data for 176 participants . At follow-up , the pain symptom score improved from median 83.3 ( 95 % confidence interval [ CI ] , 79.2 - 87.5 ) to 75.0 ( 95 % CI , 70.8 - 79.2 ) ( P<0.001 ) . The pain severity score ( 7.50 [ 95 % CI , 6.75 - 7.75 ] to 6.25 [ 95 % CI , 5.75 - 6.75 ] ) and the pain interference score ( 8.14 [ 95 % CI , 7.28 - 8.43 ] to 6.71 [ 95 % CI , 6.14 - 7.14 ] ) improved ( both P<0.001 ) , together with most social and emotional disability scores . Opioid consumption at follow-up decreased by 44 % ( P<0.001 ) . Serious adverse effects led to treatment discontinuation in 2 participants . Discussion : The treatment of chronic pain with medicinal cannabis in this open-label , prospect i ve cohort result ed in improved pain and functional outcomes , and a significant reduction in opioid use . Results suggest long-term benefit of cannabis treatment in this group of patients , but the study ’s noncontrolled nature should be considered when extrapolating the results Background : Central pain in multiple sclerosis ( MS ) is common and often refractory to treatment . Methods : We conducted a single-center , 5-week ( 1-week run-in , 4-week treatment ) , r and omized , double-blind , placebo-controlled , parallel-group trial in 66 patients with MS and central pain states ( 59 dysesthetic , seven painful spasms ) of a whole-plant cannabis-based medicine ( CBM ) , containing delta-9-tetrahydrocannabinol : cannabidiol ( THC : CBD ) delivered via an oromucosal spray , as adjunctive analgesic treatment . Each spray delivered 2.7 mg of THC and 2.5 of CBD , and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours . Results : Sixty-four patients ( 97 % ) completed the trial , 34 received CBM . In week 4 , the mean number of daily sprays taken of CBM ( n = 32 ) was 9.6 ( range 2 to 25 , SD = 6.0 ) and of placebo ( n = 31 ) was 19.1 ( range 1 to 47 , SD = 12.9 ) . Pain and sleep disturbance were recorded daily on an 11-point numerical rating scale . CBM was superior to placebo in reducing the mean intensity of pain ( CBM mean change −2.7 , 95 % CI : −3.4 to −2.0 , placebo –1.4 95 % CI : −2.0 to −0.8 , comparison between groups , p = 0.005 ) and sleep disturbance ( CBM mean change –2.5 , 95 % CI : −3.4 to −1.7 , placebo –0.8 , 95 % CI : −1.5 to −0.1 , comparison between groups , p = 0.003 ) . CBM was generally well tolerated , although more patients on CBM than placebo  reported dizziness , dry mouth , and somnolence . Cognitive side effects were limited to long-term memory storage . Conclusions : Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated Cannabinoids and opioids share several pharmacologic properties and may act synergistically . The potential pharmacokinetics and the safety of the combination in humans are unknown . We therefore undertook a study to answer these questions . Twenty – one individuals with chronic pain , on a regimen of twice – daily doses of sustained – release morphine or oxycodone were enrolled in the study and admitted for a 5–day inpatient stay . Participants were asked to inhale vaporized cannabis in the evening of day 1 , three times a day on days 2–4 , and in the morning of day 5 . Blood sampling was performed at 12–h intervals on days 1 and 5 . The extent of chronic pain was also assessed daily . Pharmacokinetic investigations revealed no significant change in the area under the plasma concentration – time curves for either morphine or oxycodone after exposure to cannabis . Pain was significantly decreased ( average 27 % , 95 % confidence interval ( CI ) 9 , 46 ) after the addition of vaporized cannabis . We therefore concluded that vaporized cannabis augments the analgesic effects of opioids without significantly altering plasma opioid levels . The combination may allow for opioid treatment at lower doses with fewer side effects UNLABELLED Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic non-cancer pain . The safety of cannabis use for medical purpose s has not been systematic ally evaluated . We conducted a prospect i ve cohort study to describe safety issues among individuals with chronic non-cancer pain . A st and ardized herbal cannabis product ( 12.5 % tetrahydrocannabinol ) was dispensed to eligible individuals for a 1-year period ; controls were individuals with chronic pain from the same clinics who were not cannabis users . The primary outcome consisted of serious adverse events and non-serious adverse events . Secondary safety outcomes included pulmonary and neurocognitive function and st and ard hematology , biochemistry , renal , liver , and endocrine function . Secondary efficacy parameters included pain and other symptoms , mood , and quality of life .  Two hundred and fifteen individuals with chronic pain were recruited to the cannabis group ( 141 current users and 58 ex-users ) and 216 controls ( chronic pain but no current cannabis use ) from 7 clinics across Canada . The median daily cannabis dose was 2.5 g/d . There was no difference in risk of serious adverse events ( adjusted incidence rate ratio = 1.08 , 95 % confidence interval = .57 - 2.04 ) between groups . Medical cannabis users were at increased risk of non-serious adverse events ( adjusted incidence rate ratio = 1.73 , 95 % confidence interval = 1.41 - 2.13 ) ; most were mild to moderate . There were no differences in secondary safety assessment s. Quality -controlled herbal cannabis , when used by patients with experience of cannabis use as part of a monitored treatment program over 1 year , appears to have a reasonable safety profile . Longer-term monitoring for functional outcomes is needed . STUDY REGISTRATION The study was registered with www.controlled-trials.com ( IS RCT N19449752 ) . PERSPECTIVE This study evaluated the safety of cannabis use by patients with chronic pain over 1 year . The study found that there was a higher rate of adverse events among cannabis users compared with controls but not for serious adverse events at an average dose of 2.5 g herbal cannabis per day Background : Chronic neuropathic pain affects 1%–2 % of the adult population and is often refractory to st and ard pharmacologic treatment . Patients with chronic pain have reported using smoked cannabis to relieve pain , improve sleep and improve mood . Methods : Adults with post-traumatic or postsurgical neuropathic pain were r and omly assigned to receive cannabis at four potencies ( 0 % , 2.5 % , 6 % and 9.4 % tetrahydrocannabinol ) over four 14-day periods in a crossover trial . Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle , followed by a nine-day washout period . Daily average pain intensity was measured using an 11-point numeric rating scale . We recorded effects on mood , sleep and quality of life , as well as adverse events . Results : We recruited 23 participants ( mean age 45.4 [ st and ard deviation 12.3 ] years , 12 women [ 52 % ] ) , of whom 21 completed the trial . The average daily pain intensity , measured on the 11-point numeric rating scale , was lower on the prespecified primary contrast of 9.4 % v. 0 % tetrahydrocannabinol ( 5.4 v. 6.1 , respectively ; difference = 0.7 , 95 % confidence interval [ CI ] 0.02–1.4 ) . Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief . Participants receiving 9.4 % tetrahydrocannabinol reported improved ability to fall asleep ( easier , p = 0.001 ; faster , p < 0.001 ; more drowsy , p = 0.003 ) and improved quality of sleep ( less wakefulness , p = 0.01 ) relative to 0 % tetrahydrocannabinol . We found no differences in mood or quality of life . The most common drug-related adverse events during the period when participants received 9.4 % tetrahydrocannabinol were headache , dry eyes , burning sensation in areas of neuropathic pain , dizziness , numbness and cough . Conclusion : A single inhalation of 25 mg of 9.4 % tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain , improved sleep and was well tolerated . Further long-term safety and efficacy studies are indicated . ( International St and ard R and omised Controlled Trial Register no. IS RCT N68314063 UNLABELLED A r and omized , double-blinded , placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis . In a crossover design , each participant was exposed to 4 single dosing sessions of placebo or to low ( 1 % tetrahydrocannabinol [ THC ] ) , medium ( 4 % THC ) , or high ( 7 % THC ) doses of cannabis . Baseline spontaneous pain , evoked pain , and cognitive testing were performed . Subjects were then administered aerosolized cannabis or placebo and the pain intensity and subjective " highness " score was measured at 5 , 15 , 30 , 45 , and 60 minutes and then every 30 minutes for an additional 3 hours . Cognitive testing was performed at 5 and 30 minutes and then every 30 minutes for an additional 3 hours . The primary analysis compared differences in spontaneous pain over time between doses using linear mixed effects models . There was a significant difference in spontaneous pain scores between doses ( P < .001 ) . Specific significant comparisons were placebo versus low , medium , and high doses ( P = .031 , .04 , and < .001 , respectively ) and high versus low and medium doses ( both P < .001 ) . There was a significant effect of the high dose on foam brush and von Frey evoked pain ( both P < .001 ) . There was a significant negative effect ( impaired performance ) of the high dose on 2 of the 3 neuropsychological tests ( Paced Auditory Serial Addition Test , Trail Making Test Part B. PERSPECTIVE This small , short-term , placebo-controlled trial of inhaled cannabis demonstrated a dose-dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain . This adds preliminary evidence to support further research on the efficacy of the cannabinoids in neuropathic pain Despite management with opioids and other pain modifying therapies , neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals . Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception . We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV . This was a phase II , double-blind , placebo-controlled , crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy ( DSPN ) . Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes ; they continued on their pre study analgesic regimens throughout the trial . Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting . Treatments were placebo and active cannabis ranging in potency between 1 and 8 % Δ-9-tetrahydrocannabinol , four times daily for 5 consecutive days during each of 2 treatment weeks , separated by a 2-week washout . The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale ( DDS ) from a pretreatment baseline to the end of each treatment week . Secondary measures included assessment s of mood and daily functioning . Of 127 volunteers screened , 
    Output:
    
Conclusions Legalizing marijuana might contribute to a modest reduction in opioid prescriptions .
Evidence about the effect of marijuana legalization on opioid overdose mortality is inconsistent and inconclusive .
If any , the effectiveness of state marijuana laws in reducing opioid overdose mortality appears to be rather small and limited to states with operational marijuana dispensaries .
It remains unclear whether the presumed benefit of legalizing marijuana in reducing opioid-related harms outweighs the policy ’s externalities , such as its impact on mental health and traffic safety