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.
Readers interested in the science of cannabis dependence and how whole cannabis smoke differs from pure THC.
Serum THC of 225 ng/mL, matching typical human levels after smoking
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
This is a well-controlled animal study using naturalistic smoke exposure and clinically relevant THC levels, but remains preclinical.
When this study was published
Published in 2016. Cannabis smoke research continues to evolve, particularly as THC potency in available products has increased.
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.
Questions still open
- Do the non-THC components of cannabis smoke modify the dependence profile? Would higher-THC cannabis produce more severe dependence?
Common questions
Does cannabis cause physical dependence?
What is the biphasic effect of cannabis?
Read the original research
Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.
PloS one, 11(4), e0153327
Citation
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
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