THC and CBD each affected brain responses to unexpected sounds differently based on cannabis use history

In less-frequent cannabis users, both THC and CBD increased mismatch negativity brain responses, but adding low-dose CBD to THC attenuated this effect, with different patterns in frequent versus less-frequent users.

Greenwood, Lisa-Marie et al.·Psychopharmacology·2022·Moderate EvidenceRandomized Controlled Trial
RTHC-03885Randomized Controlled TrialModerate Evidence2022RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Randomized Controlled Trial
Evidence
Moderate Evidence
Sample
N=36

What This Study Found

THC and CBD both increased duration and intensity MMN amplitude in less-frequent users. Low-dose CBD added to THC attenuated THC's effect on duration and intensity MMN in less-frequent users. High-dose CBD added to THC had similar attenuating effects in frequent users. The pattern of effects varied as a function of prior cannabis exposure.

Key Numbers

36 participants (18 frequent, 18 less-frequent users). 5 drug conditions. THC 8mg and CBD 400mg both increased MMN in less-frequent users. Low CBD (4mg) with THC attenuated effects in less-frequent users.

How They Did This

Randomized, double-blind, crossover placebo-controlled study with 18 frequent and 18 less-frequent cannabis users. Five vaporized drug sessions: placebo, THC 8mg, CBD 400mg, THC 8mg+CBD 4mg, THC 12mg+CBD 400mg. Multifeature MMN paradigm with duration, frequency, and intensity deviants.

Why This Research Matters

MMN is a candidate biomarker for schizophrenia linked to NMDA receptor function. Understanding how cannabinoids affect this marker helps clarify the complex relationship between cannabis and psychosis.

The Bigger Picture

The finding that CBD can modify THC's effects on brain biomarkers, but differently depending on use history, highlights the complexity of cannabinoid interactions and the importance of individual differences.

What This Study Doesn't Tell Us

Small sample (36 total). Acute effects may not reflect chronic use patterns. MMN changes may not directly relate to clinical outcomes or psychosis risk.

Questions This Raises

  • ?Do these acute neurophysiological effects predict long-term psychosis risk?
  • ?What CBD:THC ratio optimally modulates brain responses?

Trust & Context

Key Stat:
CBD attenuated THC effects on brain biomarkers, varying by use history
Evidence Grade:
Rigorous double-blind crossover design with neurophysiological measures, but very small sample.
Study Age:
Published in 2022.
Original Title:
Acute effects of Δ9-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity.
Published In:
Psychopharmacology, 239(5), 1409-1424 (2022)
Database ID:
RTHC-03885

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled TrialGold standard for testing treatments
This study
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal Study

Participants are randomly assigned to treatment or placebo groups to test cause and effect.

What do these levels mean? →

Frequently Asked Questions

What is mismatch negativity?

MMN is a brain response to unexpected sounds that reflects automatic change detection. It's reduced in schizophrenia and is linked to NMDA receptor function, making it relevant for understanding cannabis-psychosis connections.

Did CBD protect against THC effects?

Partially. Low-dose CBD combined with THC attenuated some of THC's effects on brain responses in less-frequent users. High-dose CBD had similar effects in frequent users, suggesting dose and use history both matter.

Read More on RethinkTHC

Cite This Study

RTHC-03885·https://rethinkthc.com/research/RTHC-03885

APA

Greenwood, Lisa-Marie; Broyd, Samantha J; van Hell, Hendrika H; Todd, Juanita; Jones, Alison; Murray, Robin M; Croft, Rodney J; Michie, Patricia T; Solowij, Nadia. (2022). Acute effects of Δ9-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity.. Psychopharmacology, 239(5), 1409-1424. https://doi.org/10.1007/s00213-021-05997-3

MLA

Greenwood, Lisa-Marie, et al. "Acute effects of Δ9-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity.." Psychopharmacology, 2022. https://doi.org/10.1007/s00213-021-05997-3

RethinkTHC

RethinkTHC Research Database. "Acute effects of Δ9-tetrahydrocannabinol and cannabidiol on ..." RTHC-03885. Retrieved from https://rethinkthc.com/research/greenwood-2022-acute-effects-of-9tetrahydrocannabinol

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.