Description:
<jats:p>Both the opioid heroin and the cannabinoid Δ<jats:sup>9</jats:sup>‐Tetrahydrocannabinol (Δ<jats:sup>9</jats:sup>‐THC) exhibit analgesic effects, but both drugs produce undesirable abuse liability. Abuse of opioids and cannabis is a serious global problem that affects all societies on multiple levels. However, little is known about the development of physical dependence on these two classes of drugs in primates. Thus, the aim of this study was to compare the potency of heroin‐ and Δ<jats:sup>9</jats:sup>‐THC‐induced analgesic effects and the development of physical dependence on these two drugs in rhesus monkeys. Systemic administration of either heroin (0.03–0.18 mg/kg) or Δ<jats:sup>9</jats:sup>‐THC (0.3–1.8 mg/kg) dose‐dependently produced antinociceptive effects against acute thermal nociceptive stimulus. The opioid receptor antagonist naltrexone (0.01 mg/kg) and the cannabinoid receptor antagonist SR141716A (0.3 mg/kg) produced the same degree of a rightward shift of the dose‐response curve for heroin‐ and Δ<jats:sup>9</jats:sup>‐THC‐induced antinociception, respectively. To study acute physical dependence on heroin and Δ<jats:sup>9</jats:sup>‐THC, monkeys were subjected to a short‐term repeated administration (two injections per day for 2 to 3 days) of either heroin (0.18 mg/kg) or Δ<jats:sup>9</jats:sup>‐THC (1.8 mg/kg). Then, monkeys were treated with either naltrexone (0.01 mg/kg) or SR141716A (0.3 mg/kg), i.e., antagonist‐precipitated withdrawal. We found that surgically implanted telemetric probes (DSI, model D70‐PCTR) are sensitive in detecting physiological withdrawal signs. Administration of naltrexone increased heart rate and blood pressure in heroin‐treated monkeys, indicating a fast development of physical dependence on heroin. Depending upon the duration of repeated administration of Δ<jats:sup>9</jats:sup>‐THC and the dose of SR141716A, development of physical dependence on Δ<jats:sup>9</jats:sup>‐THC can be detected too. Collectively, these results demonstrate that in nonhuman primates, systemic heroin is more potent than Δ<jats:sup>9</jats:sup>‐THC in producing antinociception, and physical dependence on heroin can occur following a short‐term exposure.</jats:p><jats:p><jats:bold>Support or Funding Information</jats:bold></jats:p><jats:p>Supported by US‐PHS grants DA‐032568 and DA‐035359.</jats:p>