Study of Δ9-THC to Treat Chronic Abdominal Pain

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The most important symptom in chronic pancreatitis (CP) is abdominal pain. Pancreatic pain is often recurrent, intense and long-lasting, and is extremely difficult to treat. Medical analgesic therapy is considered as first choice in pain management of CP, resulting in regularly prescription of opioids. The adverse consequences of prolonged opioid use, including addiction, tolerance and opioid induced hyperalgesia, call for an alternative medical treatment. Cannabis has been used to treat pain for many centuries. Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive substance of the cannabis plant, has been shown in previous studies to be a promising analgesic. The development of Namisol®, a tablet containing purified Δ9-THC showing an improved and reliable pharmacokinetic profile, provides the opportunity to test the analgesic potential of Δ9-THC in favourable conditions.

The rewarding and positive reinforcing effects of the primary psychoactive component of smoked cannabis, delta-9-tetrahydrocannabinol (THC) are mediated by the cannabinoid CB1 receptor. The CB1 receptor has also been shown to mediate cannabinoid dependence and expression of withdrawal upon cessation of drug administration, a phenomenon verified across species. This paper will review findings implicating the CB1 receptor in the behavioural effects of exogenous cannabinoids with a focus on cannabinoid dependence and reinforcement, factors that contribute to the maintenance of chronic cannabis smoking despite negative consequences. Opioidergic modulation of these effects is also discussed.

Across species, cannabinoids produce positive affective, rewarding, and reinforcing effects. Upon repeated drug administration, cannabinoid dependence develops marked by a withdrawal syndrome that is induced by either a cannabinoid antagonist or abstinence. The positive effects (reward and reinforcement) likely promote the occasional recreational use observed in cannabis abusers, whereas both the positive and negative effects of repeated use (i.e., cannabinoid dependence and withdrawal) contribute to the difficulty that a subset of cannabis smokers have achieving and maintaining abstinence. Across species the behavioural effects of cannabis, THC, and synthetic cannabinoids are clearly mediated by the endogenous cannabinoid system; the role of endogenous opioids in mediating cannabinoid effects in humans remain to be clarified.


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