COMMENTARY

Medical Marijuana: The State of the Science

Michael E. Schatman, PhD

Disclosures

February 06, 2015

In This Article

Mental Health Applications of CBD

In an early study of human experimental anxiety, Zuardi and colleagues[128] found that CBD had anxiolytic properties in participants exposed to a stressful situation.More recently, Crippa and colleagues[129] reported anxiolysis in participants receiving CBD and used single-photon emission CT to determine that this effect was mediated by the action of CBD on the paralimbic and limbic areas of the brain. Similar findings have been observed when comparing THC and CBD in healthy volunteers: THC increased anxiety in response to intensely fearsome faces and CBD reduced subjective anxiety and autonomic arousal, as measured by skin conductance response.[130]

Of greater clinical relevance, CBD was found to be superior to placebo in reducing anxiety in patients with generalized social anxiety disorder.[131] This was confirmed by another placebo-controlled trial of treatment-naive persons, which found an improvement in generalized social anxiety as measured by both subjective and physiologic parameters.[132]

A recent double-blind, placebo-controlled trial found that CBD enhanced consolidation of fear extinction when administered after extinction.[133] Collectively, these data suggest that CBD may be useful in the treatment of various anxiety disorders, including post-traumatic stress disorder.

Furthermore, CBD has been found to be superior to placebo in increasing sleep time among patients with insomnia.[134] Despite its ability to reduce anxiety and induce sleep, CBD was found to have alerting properties in a study of nocturnal sleep and early-morning behavior.[135] This paradoxical effect appears to be explained by the ability of CBD to provoke wakefulness at low doses and sedation at high doses.[136]

There is also evidence that CBD has antipsychotic effects, as demonstrated by a study finding that CBD reduced ketamine-induced depersonalization in healthy volunteers.[137] In a case report of a patient with schizophrenia who could not tolerate conventional antipsychotics, a significant reduction in psychotic symptoms was reported after administration of high-dose CBD for 4 weeks, with a return of symptoms after discontinuation.[138]

In a 4-week study of patients with Parkinson disease who presented with at least a 3-month history of psychotic symptoms, oral CBD administration resulted in a significant reduction of these symptoms.[101] A trial of patients with acute paranoid schizophrenia or schizophreniform psychosis found that CBD resulted in a decrease in psychotic symptoms similar to that experienced by the patients receiving a traditional antipsychotic agent, but with a significantly improved side effect profile.[139] These findings were confirmed in a more recent trial, with the authors attributing this effect to the potential of CBD to inhibit anandamide deactivation.[140]

In a review, Zuardi[141] asserted that "clinical studies suggest that CBD is an effective, safe and well-tolerated alternative treatment for schizophrenic patients." However, this conclusion may be premature. Although preliminary results have been promising, further larger-scale randomized controlled trials are needed in order to establish the efficacy of CBD for the treatment of psychosis.

A review by Schubart and colleagues[142] provides a more reasonable conclusion, stating that "evidence from several study domains suggests that CBD has some potential as an antipsychotic treatment." Similarly, the authors of a recent Cochrane review concluded that "there is some slight suggestion that cannabidiol may be have some antipsychotic characteristics," again calling for additional research.[143]

The potential role of CBD in the treatment of addictions is also relevant. In a recent trial, Morgan and colleagues[144] found that smokers treated with CBD reduced the number of cigarettes that they smoked by 40%; in contrast, the number of cigarettes smoked by the placebo group was unchanged.Preclinical studies have supported the ability of CBD to reduce opioid-seeking behavior and attenuate the reward-facilitating effects of opioids; however, more research is needed to fully realize the role of CBD in addiction medicine. A phase 2 study on the short-term effects of CBD on reducing drug craving in heroin-dependent persons is now under way.[145]

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