Reduced Dopamine Responses After WIN Exposure Did Not Prove a Cannabis Gateway Effect
Repeated exposure to WIN55,212-2 reduced the ability of both WIN and heroin to increase dopamine-release events in adult male rats. That neurochemical cross-tolerance did not establish that cannabis use causes people to begin or escalate heroin use.
The exposure was a synthetic cannabinoid
Rats received an escalating intravenous WIN regimen before challenge experiments. WIN is a synthetic cannabinoid-receptor agonist, not marijuana or THC. Researchers also documented reduced sensitivity to cannabinoid-like behavioral and physiological effects after the repeated regimen.
The measurement was local and specific
Fast-scan cyclic voltammetry recorded transient dopamine events in the nucleus accumbens shell of awake rats. Prior WIN treatment blunted challenge-related increases in event frequency for WIN and heroin. WIN-related amplitude changes were also affected. These were brain recordings, not blood concentrations or observations of drug choice.
Cross-tolerance is not cross-protection
A smaller dopamine response does not show reduced overdose risk, less respiratory depression or protection from addiction. Conversely, the authors’ suggestion that blunted reward signaling might encourage compensatory consumption remained a hypothesis rather than a behavior demonstrated by this experiment. The study did not measure people transitioning between drugs.
Keep the population attached to the result
Only adult male rats were studied. Age, sex, genetics, prior exposure and the brain region recorded could affect the findings. The experiment supports a particular neurochemical interaction after a particular synthetic-cannabinoid history. Applying it to THC, adolescents, women or an individual’s substance-use history requires additional evidence.
Related analysis: Similar Temperature Tolerance Did Not Make THC and JWH Cannabinoids Interchangeable.
Primary research
Chronic cannabinoid exposure produces tolerance to the dopamine releasing effects of WIN 55,212-2 and heroin in adult male rats. Neuropharmacology (2021). DOI: 10.1016/j.neuropharm.2020.108374.
