Table 1.

Comparison of Randomized Controlled Trials of Smoked Cannabis for Neuropathic Pain

	Ware et al. [45]	Wilsey et al. [47]	Ellis et al. [46]	Abrams et al. [48]
Purpose of Study	"... explore the safety and efficacy of smoked cannabis in outpatients with chronic neuropathic pain."	"... examine whether smoking cannabis produces dose-dependent analgesia on both spontaneous and evoked pain in patients with neuropathic pain."	"... ascertain a safe, clinically useful, and efficacious dosing range for smoked medicinal cannabis as a short-term analgesic in the treatment of refractory neuropathic pain in HIV DSPN."	"... determine the effect of smoked cannabis on the neuropathic pain of HIV-SN, and to determine if cannabinoids have a more general analgesic and anti-hyperalgesic effect."
Study Design	randomized, double-blind, placebo-controlled, crossover	randomized, double-blind, placebo-controlled, crossover	randomized, double-blind, placebo-controlled, crossover	randomized, double-blind, placebo-controlled
Sample Size	21	38	28	50
Pain Conditions	NP caused by trauma or surgery, with allodynia or hyperalgesia	spinal cord injury, peripheral NP, and multiple-sclerosis	HIV infection, refractory NP	HIV infection, HIV-SN
Exclusion Criteria	active substance abuse, pain due to cancer or nociceptive causes, history of psychosis, cardiac or pulmonary disease, pregnant	active substance abuse, major depressive disorder, schizophrenia, bipolar disorder, cardiovascular or pulmonary disease, never having used cannabis	active substance abuse, history of psychosis or intolerance to cannabinoids, serious medical conditions	active substance abuse, serious medical conditions, never having used cannabis
Cannabis Potency (%THC)	2.5%, 6%, 9.4%; 0% placebo	3.5%, 7%; 0% placebo	ranging from 1% to 8%; 0% placebo	3.56%; 0% placebo
Length of Study	4 phases over 8 weeks	3 sessions over ~ 4 weeks	5 study phases over 7 weeks	4 phases over 3 weeks
Findings	The 9.4% THC dose significantly decreased pain as compared to placebo. Patients also experienced improved sleep, decreased depression and anxiety as compared to placebo.	Both the 3.5% and 7% THC cannabis produced equal and significant analgesia compared to placebo. Pain was more tolerable at higher doses compared to placebo. Both doses had no effect on evoked pain or allodynia.	Pain reduction was significantly greater compared to placebo. Mood, physical disability, quality of life and sleep improved during all study treatments. The majority of patients titrated to the highest THC dose of 8%.	Patients experienced a significant decrease in pain compared to placebo. Cannabis decreased induced hyperalgesia but had little impact on heat stimulation.
Adverse Events	AE increased with potency. The most frequent complaints from the highest dose cannabis was headache, dry eyes, burning sensation, dizziness numbness and cough.	Both doses produced a general cognitive decline with the highest dose causing the greatest impairment. Both groups felt "high" or "stoned."	2 patients dropped out due to AE; 1 had a psychotic episode, 1 had respiratory irritation. AE was greater for cannabis than placebo and included cognitive impairment, fatigue, sedation, sleepiness, dry mouth, thirst.	2 patients had AE (1 dizziness; 1 anxiety) which were treated with a one-time dose of lorazepam. AE included anxiety, disorientation, confusion and dizziness.

HIV-DSPN, HIV distal sensory polyneuropathy; HIV-SN, HIV-associated sensory neuropathy; NP, neuropathic pain; AE, adverse events