Several pathologies can be regulated with positive effects by specific treatment ranges with cannabidiol (CBD), tetrahydrocannabinol (THC), or tetrahydrocannabivarin (THCV), according to systematic review findings published in Clinical Therapeutics.
Cannabis contains more than 500 different substances that include cannabinoid and noncannabinoid compounds. Barely a third of US physicians feel ready to answer cannabis questions, and almost 90% of residents and fellows feel unprepared to prescribe cannabinoids. Investigators sought to determine which cannabinoids and what range of doses have reached positive effects in treating various diseases.
They conducted a systematic review of articles in English in the ClinicalTrials.gov or PubMed databases from October 2019 through February 2020 assessing cannabinoid treatment compared with other treatment or placebo with an objective measurement assessing effectiveness. Investigators noted reviews, letters, case reports, case series, open-label trials, pilot studies, or partial-text articles were excluded. Also excluded were studies of cannabinoids administered in combination or as whole cannabis extracts, administration in healthy participants or in animals, or with inhalation or smoke as the administration vehicle.
Study participants included a wide age range of adults and children, thus dosing was reported as milligrams per kilogram of weight per day. Ultimately 55 articles were included in analysis (34 randomized clinical trials [RCTs], 11 case studies [case reports or case series], and 10 clinical studies either controlled or randomized in design but not both). None of the included studies had high risk for reporting bias, detection bias, or selection bias.
Investigators found positive effects in clinical studies for CBD 74% (range 1-50 mg/kg/d), THC 52% (range 0.01-0.5 mg/kg/d), THC-CBD 64% (mean 1:1.3 mg/kg/d [ratio 1:1]), and THCV 100% (0.2 mg/kg/d).
In 2 RCTs for cancer pain (N=796) and 1 RCT for cancer head and neck radiotherapy treatments (N=56), no significant improvements in pain or quality of life were noted with THC-CBD (mean dose 15 mg/d±0.2 mg/kg/d of THC and 14 mg/d±0.2 mg/kg/d of CBD) or THC at lower doses (1 mg/d±0.02 mg/kg/d), respectively.
Investigators noted 1 RCT (N=62) studying THCV administration in diabetes type 2 as an adjuvant therapy (0.2 mg/kg/d) showed significant improvement in pancreatic function, fasting glycemic control, apolipoprotein A, and adiponectin.
Investigators found 9 studies showing significant effects of CBD in epilepsy, reducing severity or frequency of seizures. Among 4 RCTs (N=715), mean dosing of CBD as add-on therapy was 17.5 mg/kg/d. They noted 2 prospective studies (N=150) and 1 open-label internal trial (N=162) with CBD administered as adjuvant, the mean dose of 25 mg/kg/d showed significant improvements in severity of seizure frequency, mental and social characteristics of health, and quality of life. They reported that 1 case report (N=3; adjuvant) and 1 case series (N=7; monotherapy) showed beneficial results of CBD on seizure duration, frequency, and severity, mean dose (24 mg/kg/d).
They found the most frequent adverse effects of THC at higher doses (≥0.1 mg/kg/d) were nausea, fatigue, headache, drowsiness, dizziness, and somnolence. They noted CBD was well tolerated except at higher doses (≥20 mg/kg/d). Most articles reported no adverse effects with THC-CBD.
Review limitations include the nature of review design, findings limited to oral administration, and exclusion criteria included no case reports or case series both of which were included.
Investigators concluded “most studies on THC had positive effects by using lower doses (0.01 mg/kg/d) rather than by using higher doses (0.5 mg/kg/d).” They added “However, for CBD, most studies found positive outcomes with higher doses (50 mg/kg/d) rather than with lower doses (1 mg/kg/d).” They wrote that THC-CBD’s most beneficial effects range was 1.0 (THC) to 1.3 (CBD) mg/kg/d (ratio 1:1). The most effective dosing of THCV was 0.2 mg/kg/d for adults.
Campos DA, Mendivil EJ, Romano M, García M, Martínez ME. A systemic review of medical cannabinoids dosing in human. Clin Ther. Published online November 18, 2022. doi:10.1016/j.clinthera.2022.10.003