Tolerance to the behavioral and psychological effects of THC has been demonstrated in adolescent humans and animals. The mechanisms that create this tolerance to THC are thought to involve changes in cannabinoid receptor function.One study has shown that between 2001–2002 and 2012–2013, the use of marijuana in the US doubled.Cannabis dependence develops in about 9% of users, significantly less than that of heroin, cocaine, alcohol, and prescribed anxiolytics, but slightly higher than that for psilocybin, mescaline, or LSD. Of those who use cannabis daily, 10–20% develop dependence. Withdrawal
Cannabis withdrawal symptoms occur in one-half of people in treatment for cannabis use disorders. Symptoms may include dysphoria (anxiety, irritability, depression, restlessness), disturbed sleep, gastrointestinal symptoms, and decreased appetite. It is often paired with rhythmic movement disorder. Most symptoms begin during the first week of abstinence and resolve after a few weeks. About 12% of heavy cannabis users showed cannabis withdrawal as defined by the DSM-5, and this was associated with significant disability as well as mood, anxiety and personality disorders. Cause
Cannabis addiction is often due to prolonged and increasing use of the drug. Increasing the strength of the cannabis taken and an increasing use of more effective methods of delivery often increase the progression of cannabis dependency. It can also be caused by being prone to becoming addicted to substances, which can either be genetically or environmentally acquired.
While venlafaxine has been shown to improve mood for people with cannabis use disorder, a clinical trial in this population actually found worse cannabis abstinence rates compared to placebo. It is worth noting that venlafaxine is sometimes poorly tolerated, and infrequent use or abrupt discontinuation of its use can lead to withdrawal symptoms from the medication itself, including irritability, dysphoria, and insomnia. It is possible that venlafaxine use actually exacerbated cannabis withdrawal symptoms, leading people to use more cannabis than placebo to alleviate their discomfort. Mirtazapine, which increases serotonin and norepinephrine, has also failed to improve abstinence rates in people with cannabis use disorder.People sometimes use cannabis to cope with their anxiety, and cannabis withdrawal can lead to symptoms of anxiety. Buspirone, a serotonin 1A receptor (5-HT1A) agonist, has shown limited efficacy for treating anxiety in people with cannabis use disorder, though there may be better efficacy in males than in females. Fluoxetine, a selective serotonin reuptake inhibitor, has failed to show efficacy in adolescents with both cannabis use disorder and depression. SSRIs are a class of antidepressant drugs that are also used for the treatment of anxiety disorders, such as generalized anxiety disorder. Vilazodone, which has both SSRI and 5-HT1A agonism properties, also failed to increase abstinence rates in people with cannabis use disorder.Studies of divalproex have found no significant benefit, though some studies have found mixed results. Baclofen, a GABA-B receptor agonist and antispasmodic medication, has been found to reduce cravings but without a significant benefit towards preventing relapse or improving sleep.