drug-drug interactions (Friedman & Devinsky, 2015). Current evidence also suggests that, although THC has anticonvulsive effects, at higher doses it can be proconvulsive (Detyniecki & Hirsch, 2015). However, phase III randomized controlled trials with oral CBD (Epidiolex) support efficacy and adequate safety profiles for children with Dravet syndrome (fever-induced epilepsy) and Lennox- Gastaut syndrome (childhood epilepsy) at doses of 10 and 20 mg/kg/day (O’Connell et al., 2017). In 2014, the Cochrane Collaboration (Gloss & Vickrey, 2014) published its review on cannabinoid use in epilepsy. The stated goal of the review was to evaluate the literature for human studies that explored the effect of CBD on seizure freedom for 12 months, or three times the longest usual seizure-free interval. The researchers rejected many of the studies they reviewed because they were not clinical trials. Four pioneering studies from 1980 to 1990 met all the inclusion criteria except the primary outcome. They were reviewed because they included adverse events, one of the secondary outcomes; however, the studies included inadequate numbers of participants for the drawing of conclusions. In one study, 15 patients with temporal lobe epilepsy, who experienced at least one generalized seizure weekly, received 200 mg to 300 mg of CBD daily or placebo for as long as 4.5 months. Investigators did observe that participants tolerated the CBD without toxicity. In the second study reviewed, 12 participants with uncontrolled seizures were treated with three capsules of sunflower oil (as placebo) or sunflower oil and 100 mg of CBD (300 mg daily) for the first week, followed by two capsules (200 mg daily) for three more weeks. No differences were observed in seizure frequency between the two groups, although no details were given. The only side effect was mild drowsiness. In the third study, nine participants were randomized to groups receiving either 200 mg of CBD or placebo. Participants continued to take their regular medication plus CBD or placebo for three months. Two of four participants treated with CBD were seizure-free for the three months of treatment, and none of the five participants in the placebo group experienced improvement. No adverse effects were reported. In the fourth trial, 12 participants were treated with a single-blind placebo for six months, then a double-blind dose of 300 mg of CBD or placebo in a crossover trial lasting an additional 12 months. Ten patients Glaucoma Glaucoma treatment focuses on the continuous reduction of intraocular pressure (IOP). Because marijuana smoking and THC ingestion have been found to reduce IOP by 60% to 65%, oral and topical cannabinoids show promise for future use in glaucoma treatment. The concern with smoking is that the effects on IOP last only three to four hours and the amount of smoking necessary may be prohibitive (Green, 1998). In a 2001 study, eight participants were given either two drops (50 mL) of a 25-mg or 50-mg WIN55212-2 solution or placebo solution. WIN55212-2 is a synthetic and selective CB1 receptor agonist. These drops decreased intraocular pressure within 30 minutes of application in participants with resistant glaucoma (Porcella et al., 2001). Studies continue to explore the relationship between the ECS and the pathophysiology of glaucoma as well as the long-term treatment of glaucoma with cannabinoids as hypotensive and neuroprotective agents for the eye (Cairns et Anxiety disorders Although marijuana use has been thought to be associated with a broad range of psychiatric disorders, statistical analysis has shown an association only with increased prevalence and incidence of alcohol and drug use disorders, including nicotine dependence (Blanco et al., 2016). However, marijuana use among people with anxiety or depression has been reported to be two to eight times higher than in the general population, with rates as high as 60% among people with panic symptoms (Bricker et al., 2007). Several studies suggest that marijuana, self- prescribed and smoked, or prescribed in pharmaceutical
in the trial did not experience changes in the frequency or character of seizures but reported no adverse effects. The small sample size (48 total participants) and low quality of the study designs left the authors unable to draw conclusions from the review. In an Israeli multicenter trial, 74 children (aged one to 18 years) with refractory epilepsy (resistant to more than seven drugs) were treated with marijuana oil for at least three months and an average of six months. Patients were treated with sublingual marijuana oil extract of one of two strains: “Cheese Pie” and “Avidekel,” both containing a CBD/THC ratio of 20:1, dissolved in olive oil, given three times daily. Doses ranged from two to 27 mg/kg/day. The response to treatment was evaluated as a parental-reported change in the mean monthly seizure frequency. Of the 74 patients, 66 (89%) reported reduction in seizure frequency. The reduction was 75% to 100% in 13 patients (18%), 50% to 75% in 25 (34%), 25% to 50% in nine (12%), and less than 25% in 19 (26%). Five (7%) patients reported aggravation of seizures, which led to discontinuation of use of the CBD (Tzadok et al., 2016). Researchers suggest that future studies focus on the underlying mechanisms of alterations in the ECS in chronic epilepsy and other related pathological conditions, including autism, cell type-specific boosting of the ECS (for example, ECS-based gene therapy), physiological conditions that selectively control phasic or tonic (quickly responding and more slowly responding) ECS in vivo, and cannabinoid-based prophylaxis against epileptogenesis after various forms of brain injury (Soltesz et al., 2015). Given the proven anticonvulsant effects from preclinical studies, and the lack of psychoactive properties, CBD is considered to be a promising alternative, if not a candidate as a medication, for epilepsy. Its safety record is strong to date, but the long- term effects of CBD are unknown. Researching the long-term neuropsychological effects in the developing brains of children is particularly important. Perhaps the bottom line at this time remains, that randomized trials with large cohorts are needed, as some studies continue to find no evidence of efficacy for CBD: THC products in treating epilepsy, sleep, or behavior in certain study populations (Devinsky et al., 2022). al., 2016). It is worth noting that Miller and colleagues (2018) found that, although THC reduces IOP, CBD seems to have the opposite effect. The UK Biobank is a large-scale biomedical database and research resource, containing in-depth genetic and health information from half a million UK participants. In one of their recent clinical trials, they found that while inhaling cannabis smoke is injurious to the eye, in the case of glaucoma the manifestations are different from those of inhaled tobacco smoke. Cannabis reduces intraocular pressure but accelerates glaucoma development. Cannabis does not increase the risk of glaucoma, while cigarette smoking increases risk of glaucoma and significantly accelerates glaucoma development. Apparently, early use of cannabis does lead to the earlier development of glaucoma, however (Lehrer & Rheinstein, 2022). form, may be effective in treating symptoms related to anxiety. However, a review of the literature found that marijuana used in self-medication as a sedative can also be a “cause of anxiety disorders” (Vorspan et al., 2015, p. 4). Another review of the literature suggested that frequent users of marijuana consistently had a high prevalence of anxiety disorders and people suffering from an anxiety disorder have often used marijuana. It was not clear from existing data if marijuana use increased the risk of developing long-lasting anxiety disorders
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