The first such study evaluated lofexidine, an agonist at the alpha2-adrenergic receptor that is used to treat opiate withdrawal [46]. Lofexidine was tested both alone and in combination with THC [47]. Eight non-treatment-seeking male regular cannabis users were maintained on each of four medication conditions double-blind: placebo, THC (60 mg/day), lofexidine (2.4 mg/day), and THC (60 mg/day) combined with lofexidine (2.4 mg/day). THC reversed the anorexia and weight loss associated with cannabis withdrawal, and decreased some withdrawal symptoms, but increased sleep onset latency, and did not decrease the resumption of cannabis use when active cannabis was available. Lofexidine, which was sedating, worsened withdrawal-related anorexia and did not robustly attenuate mood symptoms associated with withdrawal, but improved sleep and decreased cannabis relapse. The combination of lofexidine and THC produced the most robust improvements in sleep and decreased cannabis withdrawal, craving, and relapse in daily cannabis smokers relative to either medication alone.
