There have been numerous clinical trials demonstrating the medical benefits of cannabis and cannabinoids, including the major psychoactive compound Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
There are several cannabinoid-based medications that have been approved by the FDA and Health Canada:
Nabiximols (Sativex®) is a whole plant cannabis extract with a 1:1 ratio of THC and CBD, and also contains minor terpenoids. It is taken orally as an oral-mucosal spray.
Nabilone (Cesamet®) is a synthetic analogue of THC. It is taken orally as capsules.
Dronabinol (Marinol®) is a synthetic form of THC taken orally as capsules.
Cannabinoids are recommended as third-line agents in the management of chronic neuropathic pain (1), based on increasing evidence of efficacy in patients with multiple sclerosis (2-6), HIV neuropathy (7, 8), post-traumatic and postsurgical neuropathy (9), painful diabetic neuropathy (10-12), neuropathic pain from spinal cord injury (13, 14), allodynia (15), fibromyalgia (16) and other conditions (11, 17). Cannabinoids significantly reduced neuropathic pain of various etiologies in individuals already receiving analgesic drugs (2, 7-11, 13, 18, 19).
Importantly, cannabinoids augment the analgesic effects of opioids, without significantly altering blood opioid levels (19). This may allow for opioid treatment at lower doses with fewer side effects (19).
Smoked/vaporized whole plant cannabis has been shown to relieve pain in patients with HIV neuropathy, postsurgical neuropathy, spinal cord injury neuropathy and painful diabetic neuropathy in randomized, double blind, placebo-controlled trials (7-11, 13, 18, 19).
Nabiximols (Sativex®) has been shown to significantly reduce neuropathic pain of patients with multiple sclerosis (2, 3), allodynia (15) and spinal cord injury (14) in randomized, placebo-controlled, double blind crossover and parallel studies. Nabiximols may be effective for treating pain caused by rheumatoid arthritis (20).
Nabilone (Cesamet®) has been shown to ameliorate neuropathic pain associated with multiple sclerosis (4, 5), diabetes (12) and other conditions (17).
Dronabinol (Marinol®) has been shown to ameliorate neuropathic pain in 2 randomized, placebo-controlled trials (6, 21), and provide pain relief for patients suffering from moderate to severe continuous pain due to advanced cancer (22, 23).
Cannabinoids are effective as an adjunctive treatment for the symptomatic relief of spasticity and neuropathic pain in adults with multiple sclerosis (2-6, 24-37).
Smoked/vaporized whole plant cannabis has been shown to relieve symptoms associated with MS, in a double-blind, placebo-controlled, crossover trial (31).
Nabiximols (Sativex®) has been investigated in phase 2 and phase 3 double blind, randomized, placebo-controlled trials to ameliorate spasticity and neuropathic pain, and improve sleep quality in patients with multiple sclerosis (2, 3, 27-30).
Nabilone (Cesamet®) as an adjunctive to gabapentin is an effective, well-tolerated combination for MS-induced neuropathic pain (4, 5).
Dronabinol (Marinol®) has been investigated in several randomized, placebo-controlled trials for treatment of multiple sclerosis associated spasticity and pain, and slowing MS disease progression (6, 32, 34, 36, 37).
Post Traumatic Stress Disorder
Nabilone (Cesamet®) There have been 2 small open-label, non-placebo-controlled trials that study the effects of nabilone for PTSD related symptoms (38, 39). Nabilone provided significant relief for patients with PTSD with 72% of patient’s self-reported total cessation or lessening of severity of nightmares. Other self-reported benefits included an improvement in sleep time, a reduction in daytime flashbacks, and cessation of night sweats.
Cannabis Resin Extract: A case report describes a 19-year-old male patient, a victim of abuse with a spectrum of severe PTSD symptoms, including intense flashbacks, panic attacks, self-mutilation and several suicide attempts, found that some of his major symptoms were dramatically reduced by smoking cannabis resin from Turkey, and assumed to contain high amounts of THC and a nearly equivalent amount of CBD (41).
Cannabinoids have shown improvement in symptom presentation in patients with epilepsy whose symptoms were unaffected by conventional therapy (42, 43).
Cannabidiol (Epidiolex®) is 1:20 blend of low THC/high CBD taken orally and has been shown to reduce seizure frequency and seizure load in children with treatment-resistant epilepsy in an open-label intervention trial (43) and retrospective cohort study (42).
Inflammatory Bowel Disease
Smoked/vaporized whole plant cannabis: Two small preliminary trials have shown that smoked cannabis may improve IBD patient’s weight gain, physical pain, diarrheal symptoms, depression, social functioning, and ability to work (44, 45).
HIV/AIDS related symptoms
Cannabinoids are effective for treating painful HIV-associated sensory neuropathy (7, 8) and are recommended as third-line agents in the management of chronic neuropathic pain (1). Cannabinoids can help patients with HIV increase caloric intake (46), improve body weight, improve sleep (47), reduce pain (7) and improve mood (46).
Smoked whole plant cannabis can help patients with HIV increase caloric intake (46), improve body weight, improve sleep (47), reduce pain (7) and improve mood (46).
Dronabinol (Marinol®) has been shown to help patients with HIV, AIDS (48) and late stage AIDS improve appetite, maintain body weight and improve mood (48, 49).
Patients with fibromyalgia use cannabis or cannabinoids to improve a myriad of symptoms, including pain, anxiety and sleep (50, 51).
Nabilone (Cesamet®): In a randomized, double-blind, placebo-controlled trial, 40 patients with fibromyalgia treated with nabilone had significant improvements in Visual analog scales of pain, Fibromyalgia Impact Questionnaire scores, and anxiety scores compared with placebo (52). Nabilone has also been shown to help patients with fibromyalgia improve sleep (53).
Dronabinol (Marinol®) use in patients with fibromyalgia provided statistically significant relief of pain, stiffness, relaxation, somnolence and perception of well-being, evaluated by VAS before and 2 hours after administration (16).
In an observational trial, 120 adults with migraine for whom cannabis prophylaxis was recommended, and of which 67.8% had previously used cannabis, the frequency of headache diminished from 10.4 to 4.6 attacks per month (p < 0.0001). Overall, 85.1% had decreased migraine frequency, with 39.7% reporting positive effects: prevention of or reduced headache frequency (19.8%) or aborted headache (11.6%) (54).
Cancer related symptoms
Chemotherapy-induced nausea and vomiting is a major problem in cancer patients, with nausea being one of the most stressful reported events (55). Cannabinoids, including THC have been shown to reduce emetic events and severity of nausea in patients undergoing chemotherapy and radiation therapy (24, 56).
A systematic review of 30 clinical trials involving orally administered synthetic THC (nabilone and dronabinol) showed cannabinoids were superior to dopamine receptor antagonists in preventing chemotherapy-induced nausea and vomiting (57).
Adjunct therapy with cannabinoids has been shown to provide pain relief in patients with advanced cancer not attaining pain relief with current medications (58, 59).
Nabilone (Cesamet®): Nabilone has been shown to be effective for helping patients suffering from chemotherapy-induced nausea and vomiting (57). Nabilone may also help patients with cancer improve mood, appetite, anxiety and pain, as well as reduce polypharmacy (60).
Nabiximols (Sativex®): Nabiximols have been shown to help patients suffering from chemotherapy-induced nausea and vomiting (56), and intractable cancer-related pain (58, 59).
Note: There is some evidence that cannabis-based medicines may be effective in treating nausea and vomiting in children during chemotherapy. In a clinical trial in Israel, 8 children (3-13 years) with cancer were treated orally with Δ8-THC (up to 0.64 mg/kg/dose, dissolved in edible oil; not currently available for therapeutic use), to allay nausea during chemotherapy. Δ8-THC has lower psychotropic potency than the main cannabis constituent Δ 9-THC. The treatment started 2h before each antineoplastic treatment and was continued every 6 hrs for 24 hours. After a total of 480 treatments, the only side effects reported were slight irritability in two of the youngest children (3.5 and 4 years old); both acute and delayed nausea and vomiting were controlled (61).
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