Source/Disclosures
Disclosures: Howes reports grants from Angellini, AstraZeneca, Autifony, Biogen, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Rand, Recordati, Roche and Sunovion. Please see the study for all other authors’ relevant financial disclosures. The editorial authors report no relevant financial disclosures.
March 23, 2020
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THC linked to psychiatric symptoms with large effect sizes

Source/Disclosures
Disclosures: Howes reports grants from Angellini, AstraZeneca, Autifony, Biogen, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Rand, Recordati, Roche and Sunovion. Please see the study for all other authors’ relevant financial disclosures. The editorial authors report no relevant financial disclosures.
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Oliver Howes

A single administration of tetrahydrocannabinol, or THC, induced psychiatric symptoms with large effect sizes, according to results of a systematic review and meta-analysis published in The Lancet Psychiatry.

“These findings highlight a potential risk of taking THC-containing cannabis products, and, importantly, show that THC can lead to short-term psychotic symptoms even in people with no history of mental illness or other risk factors,” Oliver D. Howes, MRCPsych, PhD, professor of molecular psychiatry at King’s College London, told Healio Psychiatry.

More than 150 years ago, research showed an association between psychotic symptoms and cannabis use, and subsequent independent studies have explored the psychotomimetic properties of THC. Most of these studies supported the original findings; however, certain discrepancies have highlighted the need to determine the magnitude and consistency of these effects. Moreover, potential effect modifiers, including age, sex, type of THC and dose, have yet to be systematically evaluated.

Howes and colleagues aimed to investigate the effect of THC alone and in combination with cannabidiol (CBD) compared with placebo on psychiatric symptoms among healthy individuals. They searched three databases for studies published in English through May 21, 2019, that featured a within-person, crossover design. They included studies that reported symptoms using the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS) after the acute administration of nasal, oral or IV THC, CBD and placebo among healthy participants. Researchers also selected studies with data that allowed calculation of standardized mean change scores for positive symptoms, such as hallucinations and delusions; negative symptoms, such as blunted affect and amotivation; and general symptoms, such as depression and anxiety.

The investigators conducted a random-effects meta-analysis to assess the main outcomes of the effect sizes for positive, negative and total BPRS and PANSS scores measured in healthy participants after THC administration vs. placebo. They systematically reviewed the effects of CBD but did not include this outcome in a meta-analysis because the number of studies on its moderating effects was insufficient.

Howes and colleagues identified 15 eligible studies that involved the acute administration of THC and four studies on CBD plus THC administration. Results of the meta-analysis showed THC significantly increased total symptom severity with a large effect size (standardized mean change [SMC] = 1.1; 95% CI, 0.92-1.28); positive symptom severity (SMC = 0.91; 95% CI, 0.68-1.14); and negative symptom severity with a large effect size (SMC = 0.78; 95% CI, 0.59-0.97). Of the four studies in the systematic review that evaluated the effects of CBD on THC-induced symptoms, only one identified a significant reduction in symptoms.

“I was surprised that THC induced other psychiatric symptoms, such as social withdrawal, as well as psychotic symptoms, and that tobacco was associated with less effects, although this shouldn't be taken as suggesting tobacco protects against the effects of THC,” Howes told Healio Psychiatry.

In a related editorial, Carsten Hjorthøj, PhD, MSc, and Christine Merrild Posselt, PhD, both of Copenhagen Research Center for Mental Health, contextualized the importance of this research.

“This growing scientific consensus is not reflected in the mainstream public discourses, which have a major effect on the political agenda to decriminalize or legalize cannabis,” they wrote. “It also appears that, in many places (eg, several U.S. states), the first thing to be legalized is medicinal cannabis followed by increasing decriminalization and sometimes complete legalization of cannabis. It is thus of utmost importance that the public and politicians are informed of the most up-to-date evidence on cannabis.” – by Joe Gramigna

Disclosures: Howes reports grants from Angellini, AstraZeneca, Autifony, Biogen, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Rand, Recordati, Roche and Sunovion. Please see the study for all other authors’ relevant financial disclosures. The editorial authors report no relevant financial disclosures.