The Pharmacokinetics, Efficacy, and Safety of a Novel Selective-Dose Cannabis Inhaler in Patients With Chronic Pain: A Randomized, Double-Blinded, Placebo-Controlled Trial

Background: Precise cannabis treatment dosing remains a major challenge, leading to physicians’ reluctance to prescribe medical cannabis.

Objective: To test the pharmacokinetics, analgesic effect, cognitive performance, and safety effects of an innovative medical device that enables the delivery of inhaled therapeutic doses of Δ⁹-Tetrahydrocannabinol (THC) in patients with chronic pain.

Methods: In a randomized, 3-arms, double-blinded, placebo-controlled, cross-over trial, 27 patients received a single inhalation of Δ⁹ -THC: 0.5mg, 1mg, or a placebo. Δ⁹ -THC plasma levels were measured at baseline and up to 150-minutes post-inhalation. Pain intensity and safety parameters were recorded on a 10-cm visual analogue scale (VAS) at pre-defined time points. Cognitive performance was evaluated using the selective sub-tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Results: Following inhalation of 0.5mg or 1mg, Δ⁹ -THC plasma C_max ±SD were 14.3±7.7 and 33.8±25.7 ng/ml. T_max ±SD were 3.7±1.4 and 4.4±2.1 minutes, and AUC₀ →_infinity ±SD were 300±144 and 769±331 ng*min/ml respectively. Both doses, but not the placebo, demonstrated a significant reduction in pain intensity compared with baseline and remained stable for 150-minutes. The 1mg dose showed a significant pain decrease compared to the placebo. Adverse events were mostly mild and resolved spontaneously. There was no evidence of consistent impairments in cognitive performance.

Conclusion: This feasibility trial demonstrated that a metered-dose cannabis inhaler delivered precise and low THC doses, produced a dose-dependent and safe analgesic effect in patients with neuropathic pain/ complex-regional pain syndrome (CRPS). Thus, it enables individualization of medical cannabis regimens that can be evaluated pharmacokinetically and pharmacodynamically by accepted pharmaceutical models.