Rats Exposed to Cannabis Smoke Developed Dependence and Showed a Two-Phase Effect on Activity
Rats exposed to cannabis smoke at clinically relevant THC levels showed a biphasic activity pattern (brief increase then prolonged decrease), developed physical dependence, and the activity reduction involved CB1 receptors.
Quick Facts
What This Study Found
Researchers exposed rats to actual cannabis smoke (not just THC) to study behavioral effects, including whether it produces dependence.
Cannabis smoke caused a biphasic effect on locomotor activity: a brief increase followed by a prolonged decrease in movement and rearing behavior. The CB1 receptor antagonist rimonabant increased activity and prevented the smoke-induced decrease in rearing, confirming CB1 receptor involvement.
In a larger open field and elevated plus maze, smoke-exposed rats showed increased activity and spent more time in the center zone, suggesting reduced anxiety. Importantly, chronic cannabis smoke exposure produced physical dependence: rimonabant-precipitated withdrawal produced more somatic signs in smoke-exposed rats than air-control rats.
Serum THC levels after smoke exposure (225 ng/mL) were similar to levels found in humans after smoking cannabis.
Key Numbers
Serum THC: 225 ng/mL after smoke exposure (similar to human levels). Cannabis smoke produced biphasic locomotor effects. Rimonabant precipitated more withdrawal signs in smoke-exposed rats. CBD and other cannabinoids were present in the smoke alongside THC.
How They Did This
Cannabis cigarettes containing 5.7% THC were burned in a smoking machine. Rats were tested in small and large open fields and the elevated plus maze. CB1 antagonist rimonabant was used to probe receptor involvement and precipitate withdrawal. Anandamide effects were also tested. Serum THC was measured.
Why This Research Matters
Most cannabis research uses purified THC rather than actual cannabis smoke, which contains many other compounds. This study used smoke exposure that produced clinically relevant blood THC levels, making it more translatable. The demonstration of physical dependence from smoke exposure adds to evidence that cannabis can produce physiological dependence.
The Bigger Picture
This study bridges the gap between human cannabis smoking and animal research by using actual cannabis smoke rather than isolated THC. The confirmation of physical dependence from naturalistic smoke exposure strengthens the evidence that cannabis dependence has a physiological basis.
What This Study Doesn't Tell Us
Rats were exposed passively to smoke, which differs from voluntary human smoking. The cannabis cigarettes contained a specific THC concentration (5.7%) that may differ from current commercially available cannabis. Behavioral effects in rats do not directly translate to human subjective experience. The dependence model used precipitated withdrawal, which may overestimate the severity of spontaneous withdrawal.
Questions This Raises
- ?Do the non-THC components of cannabis smoke modify the dependence profile?
- ?Would higher-THC cannabis produce more severe dependence?
Trust & Context
- Key Stat:
- Serum THC of 225 ng/mL, matching typical human levels after smoking
- Evidence Grade:
- This is a well-controlled animal study using naturalistic smoke exposure and clinically relevant THC levels, but remains preclinical.
- Study Age:
- Published in 2016. Cannabis smoke research continues to evolve, particularly as THC potency in available products has increased.
- Original Title:
- Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.
- Published In:
- PloS one, 11(4), e0153327 (2016)
- Authors:
- Bruijnzeel, Adriaan W(4), Qi, Xiaoli, Guzhva, Lidia V, Wall, Shannon, Deng, Jie V, Gold, Mark S, Febo, Marcelo, Setlow, Barry
- Database ID:
- RTHC-01114
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Does cannabis cause physical dependence?
This study found that rats chronically exposed to cannabis smoke showed physical withdrawal signs when given a CB1 receptor blocker, providing evidence of physiological dependence. In humans, cannabis withdrawal syndrome is a recognized clinical entity with symptoms including irritability, sleep disruption, and anxiety.
What is the biphasic effect of cannabis?
Cannabis smoke produced a brief increase in activity followed by a longer decrease. This two-phase pattern is consistent with some human experiences of initial stimulation followed by sedation, and may reflect different receptor populations or signaling pathways being activated at different time points.
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Cite This Study
https://rethinkthc.com/research/RTHC-01114APA
Bruijnzeel, Adriaan W; Qi, Xiaoli; Guzhva, Lidia V; Wall, Shannon; Deng, Jie V; Gold, Mark S; Febo, Marcelo; Setlow, Barry. (2016). Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.. PloS one, 11(4), e0153327. https://doi.org/10.1371/journal.pone.0153327
MLA
Bruijnzeel, Adriaan W, et al. "Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.." PloS one, 2016. https://doi.org/10.1371/journal.pone.0153327
RethinkTHC
RethinkTHC Research Database. "Behavioral Characterization of the Effects of Cannabis Smoke..." RTHC-01114. Retrieved from https://rethinkthc.com/research/bruijnzeel-2016-behavioral-characterization-of-the
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.