Single Dose Of THC Could Trigger Psychiatric Symptoms In Healthy Adults

A single dose of tetrahydrocannabinol (THC), the psychoactive component in cannabis, may induce psychotic, depressive, and anxiety symptoms in healthy adults, according to a systematic review. A single dose is roughly equivalent to smoking one marijuana joint.

"This risk needs to be considered before prescribing THC-containing products such as medical marijuana," Dr. Oliver Howes of King's College London, UK, told Reuters Health by email.

As reported in The Lancet Psychiatry, the systematic review was based on 15 studies including 331 people with no history of psychotic or other major psychiatric disorders. The studies investigated participants' psychiatric symptoms following acute administration of intravenous, oral, or nasal THC, cannabidiol (CBD), and placebo, as measured by the Brief Psychiatric Rating Scale and the Positive and Negative Syndrome Scale.

Scores for an increase in severity of positive psychotic symptoms (including delusions and hallucinations); negative psychotic symptoms (such as blunted affect and amotivation); and general symptoms (including depression and anxiety) were compared.

THC doses ranged from 1.25 mg to 10 mg, leading to peak THC blood levels of 4.56 to 5.1 ng/mL when orally administered and 110-397 ng/mL when injected or inhaled. These concentrations are comparable to those seen shortly after smoking typical cannabis joint containing 16-34 mg of THC.

Compared to placebo, THC significantly increased total symptom severity and negative symptom severity with large effect sizes, as well as the severity of positive psychotic symptoms. Effect sizes remained significant regardless of sex, age, dose, route of administration, prior cannabis use and tobacco use.

However, intravenous THC induced more severe positive symptoms than did inhaled THC. There were insufficient studies to assess the effect of oral THC.

Further, there was a negative association between tobacco smoking and positive symptoms induced by THC. Dr. Howes said this finding "highlights an interesting interaction between THC and tobacco for future studies to investigate."

An analysis of four studies (too few for a meta-analysis) found no consistent evidence that CBD induces psychiatric symptoms itself or that it moderates THC's effects in healthy individuals.

"We recently published findings that the protein that THC binds to in the brain, the cannabinoid receptor 1, is lower in people with psychosis," Dr. Howe noted. (https://bit.ly/2UA0IpS) "Our future research aims to understand how THC and other cannabinoids might act on this protein to lead to psychotic symptoms."

Dr. Carsten Hjorthoj of the University of Copenhagen, coauthor of a related editorial, commented in an email to Reuters Health, "Clinicians, patients, and the general public should be aware that THC, even in low doses such as those found in medical marijuana, may not be at all unproblematic, and that special care should be taken in not overestimating the potential benefits of CBD."

—Marilynn Larkin

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