Only Half of Healthy Volunteers Experienced Psychotic Symptoms From THC, and Their Brains Responded Differently | Research

The takeaway

When 21 healthy men received 10 mg oral THC, about half experienced transient psychotic symptoms while the other half did not, and fMRI revealed distinctly different brain activation patterns between the two groups.

Read this if you have had psychotic-like experiences from cannabis and want to understand why some people are more susceptible.

THC had opposite effects on brain activation in susceptible vs. non-susceptible individuals

What the researchers found

In a double-blind, placebo-controlled study, 21 healthy men with minimal cannabis experience received 10 mg oral THC or placebo. About half (n=11) developed transient psychotic symptoms while the remainder (n=10) did not. The group experiencing psychotic symptoms made more inhibition errors and showed different brain activation in the left parahippocampal gyrus, bilateral middle temporal gyri, and right cerebellum.

Remarkably, THC had opposite effects on brain activation in the two groups in these regions. The psychosis-prone group also showed less activation in temporal and cerebellar regions independent of THC, suggesting pre-existing neural differences.

Why it matters

This was the first demonstration that individual differences in sensitivity to THC's psychosis-inducing effects have a measurable neural basis. The finding that about half of participants experienced psychotic symptoms while the other half did not, with corresponding brain differences, helps explain why cannabis affects people so differently.

The numbers in context

21 healthy men. 10 mg oral THC. 11 developed transient psychosis, 10 did not. Differential activation in parahippocampal gyrus, middle temporal gyri, and cerebellum. THC had opposite directional effects on brain activation in the two groups.

How the study worked

Double-blind, placebo-controlled, pseudorandomized design. 21 healthy men with minimal cannabis experience received 10 mg oral THC or placebo. fMRI recorded during a go/no-go inhibition task. Participants split into transiently psychotic (n=11) and non-psychotic (n=10) groups based on PANSS positive scores after THC.

What this study cannot tell us

Small sample size (21 subjects). Only men were studied. The post-hoc split into groups based on symptom response means the groups were not randomly assigned. Minimal cannabis experience may not reflect how regular users respond. A single dose does not model chronic exposure.

How to read the evidence

Controlled experimental study with fMRI, but small sample and post-hoc grouping; moderate evidence.

When this study was published

Published in 2013. Research on individual vulnerability to THC-induced psychosis has continued with genetic and neuroimaging approaches.

The bigger picture

This study provides biological evidence for what cannabis users have long known: the drug affects people very differently. The neural differences between susceptible and non-susceptible individuals may eventually help identify who is at risk for cannabis-related psychotic experiences.

Questions still open

Can the neural differences between susceptible and non-susceptible individuals be detected before cannabis exposure? Would these findings replicate in women? Do people who experience transient THC-induced psychosis have higher long-term psychosis risk?

Common questions

Why does cannabis cause psychotic symptoms in some people but not others?

This study found that people who experienced THC-induced psychotic symptoms had different brain activation patterns in the temporal cortex and cerebellum, even before taking THC. This suggests pre-existing neural differences make some brains more susceptible to THC's psychosis-inducing effects.

Is experiencing psychosis from cannabis permanent?

In this study, the psychotic symptoms were transient, resolving after the drug wore off. However, experiencing transient psychotic symptoms from cannabis may indicate underlying vulnerability. Research suggests that repeated cannabis-induced psychotic experiences could increase the risk of developing a lasting psychotic disorder in susceptible individuals.

Read the original research

Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers.

Psychological medicine, 43(6), 1255-67

View on PubMed ↗Publisher’s paper ↗

Citation

Atakan, Z; Bhattacharyya, S; Allen, P; Martín-Santos, R; Crippa, J A; Borgwardt, S J; Fusar-Poli, P; Seal, M; Sallis, H; Stahl, D; Zuardi, A W; Rubia, K; McGuire, P. (2013). Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers.. Psychological medicine, 43(6), 1255-67. https://doi.org/10.1017/S0033291712001924