CBD Pretreatment Worsened Delayed Recall in a Schizophrenia Cannabis Challenge

In a randomized crossover experiment involving patients with schizophrenia-spectrum illness and cannabis use disorder, CBD pretreatment did not protect against a cannabis challenge. Delayed verbal recall was worse after CBD than after placebo pretreatment.

The population and sequence were specific

Chesney and colleagues studied clinically stable patients taking antipsychotic medication who regularly used cannabis. Thirty completed both 20 mg THC challenge sessions per protocol. Participants received 1,000 mg oral CBD or matching placebo, then inhaled vaporized cannabis three hours later.

Some nonresponders completed additional higher-dose challenges, but those sessions should not be confused with the primary 30-person comparison. The sample was predominantly male, and all per-protocol participants met criteria for cannabis use disorder.

The primary memory comparison favored placebo pretreatment

Mean delayed-recall scores were 3.5 after CBD and 4.8 after placebo pretreatment. The mean difference was −1.3, with a 95% confidence interval from −2.0 to −0.6 and p = 0.001. Lower scores indicated worse recall.

The authors also reported greater positive psychotic symptoms with CBD, while negative symptoms and several other outcomes did not differ significantly. Thus, neither a universal adverse effect across every measure nor a protective effect describes the pattern accurately.

More circulating THC did not explain the finding

Pharmacokinetic analyses found no evidence that CBD increased plasma exposure to THC or its active 11-hydroxy metabolite under this protocol. That null result argues against assuming that every CBD–THC interaction operates by raising those concentrations. It does not prove a particular alternative biological mechanism.

Two treatment-related adverse events occurred following CBD pretreatment, including one episode of persecutory delusions that resolved by the next day. The study was too small to estimate uncommon-event rates reliably. Its acute challenge design also cannot establish long-term effects of CBD treatment without a cannabis challenge.

These findings should not be generalized to every person with psychosis or every cannabinoid formulation. They directly limit the claim that CBD necessarily buffers cannabis effects in this patient group. Our discussion of CBD outcome interpretation explains why the population, treatment sequence and comparator must remain part of the conclusion.

Primary research

Edward Chesney and colleagues. Neuropsychopharmacology (2025). Does cannabidiol reduce the adverse effects of cannabis in schizophrenia? A randomised, double-blind, cross-over trial.