These doses are far higher than could be achieved by systemic administration of these cannabinoids and would also be associated with significant psychoactive effectsReference 1328. An in vivo study examining the anti-neoplastic effects of CBG on colon carcinogenesis found that CBG (3 and 10 mg/kg CBG) inhibited xenografted colon cancer cell growth by 45%Reference 1321. One study examined the effect of combining THC, CBD and radiotherapy in a mouse model of gliomaReference 1323. In this study, combining THC and best CBD gummies CBD (100 µmol/L each) was associated with a reduction in tumour progression and further addition of irradiation to the combination cannabinoid treatment was associated with further reduction in tumour growthReference 1323. An in vivo study of the effects of THC in skin cancer reported that doses of 5 mg/kg THC/day (s.c.) significantly reduced the growth of HCmel12 melanomas but not B16 melanomasReference 1320.
This study was followed up by a six-week, randomized, double-blind, placebo-controlled trial by the same research group. The authors reported a significant difference in tic reduction compared to placebo in some patients, and no detrimental effects on neuropsychological performance during or after treatment with 10 mg doses of Δ9-THCReference 252. The major limitations of all three clinical studies were their small sample size and their relatively short duration. Frequent adverse effects, likely caused by cannabis, included drowsiness, fatigue, dizziness, dry mouth, nausea and cognitive effects that were generally mild to moderate in severity and generally well tolerated. Serious adverse effects included urinary tract infection, head injury, and interstitial lung disease (oral cannabis extract), delirium (nabilone), and suicidal ideation and disorientation (oral mucosal cannabis spray).
Dosing of nabilone was 0.5 mg, 1 h prior to bedtime; effective dose range was 0.2 mg to 4 mg nightly with all doses kept below 6 mg daily. Treatment arms lasted for seven weeks each, with a two-week washout period in between. Half (50%) of the subjects reported a significant improvement in nightmare suppression on nabilone, while only 11% of subjects reported improvement with placebo. Anecdotal and case-reports have suggested amelioration of symptoms associated with TS when smoking cannabisReference 257Reference 260. In contrast to healthy cannabis users, neither a 5 mg nor a 10 mg dose of Δ9-THC caused cognitive impairment in patients with TS.
Furthermore, the anti-neoplastic effect was found to be CB receptor-dependent. Furthermore, doses of THC and CBD of 4 mg/kg each delivered systemically and 100 mg/kg CBD delivered orally were reported to sensitize tumours to first line agents in mouse xenograft models that more closely resemble primary tumour growthReference 1329.
Taken together, these studies suggest that cannabinoids such as Δ9-THC and CBD can, at least under a specific set of circumstances, have anti-neoplastic effects in various animal models of cancer at certain dose ranges. An enriched-enrolment, randomized-withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone (1 – 4 mg/day), as an adjuvant in the treatment of diabetic peripheral neuropathic pain, reported statistically significant improvements in sleep and overall patient statusReference 612. A two-week, randomized, double-blind, active-control, crossover study of 29 patients suffering from fibromyalgia reported that nabilone (0.5 – 1.0 mg before bedtime) improved sleep in this patient populationReference 597. An open-label, non-placebo-controlled trial of nabilone for PTSD reported that nabilone treatment was associated with an improvement in sleep time, cessation or lessening of nightmare severity, and cessation of night sweatsReference 578.