AIDS Wasting
One of the few broadly recognized legal medical uses of cannabinoids is in the treatment of wasting due to AIDS, cancer chemotherapy, and severe anorexia. The primary active constituent of cannabis, THC, has the interesting honor of appearing on the DEA’s scheduling twice. THC is scheduled once in the list of most dangerous drugs with no known accepted medical use (Schedule I) as “Tetrahydro- cannabinols: THC, Delta-8 THC,
Delta-9 THC and others” and again as less dangerous with only moderate abuse potential and accepted medical use (Schedule III) as “Dronabinol: Marinol, synthetic THC” (13, 14, 15). A chemical cannot magically change pharma- codynamic or pharmacokinetic properties just because it originates from a man made process and not biosynthesis. On a purely molecu- lar level, our bodies cannot distin- guish between the two sources. I don't know about you, but to me, the current insistence that THC has two legitimate schedules seems like a pretty delusional stance to take. Regardless of this insanity, doctors in the USA are federally allowed to prescribe Marinol to those suffer- ing from AIDS wasting syndrome. Where therapeutic cannabis laws have been enacted, these patients may also utilize preparations of cannabis to help reduce the nausea and stimulate the poor appetite associated with AIDS wasting. In 2005, Woolridge, et al. collected data from 520 HIV patients attend- ing a large clinic and collected sta- tistics on rates of cannabis use, reported reasons for use, and whether or not the patient felt cannabis improved symptoms. Use of cannabis to control symptoms was reported by 27% (143) of those who completed the question- naire. Of these 143 cannabis using patients, 97% experienced appetite stimulation and 93% reduced nau- sea (12). This finding is not surpris- ing considering that anandamide, one of the primary endocannabi- noids, helps to maintain healthy serotonin and dopamine levels, feeding behaviors, and cognitive functioning during periods of diet reductions like those seen in wast- ing syndromes (16). Anandamide is also involved in the initiation of feeding behaviors by means of CB1 cannabinoid receptor activation in the hypothalamus (17). It is this involvement of the endocannabi- noid system in the regulation of feeding behaviors that explains
why cannabis and THC stimulate appetite and combat wasting. Several studies have investigated how effectively both Marinol and standardized cannabis improve signs of wasting in HIV positive individuals. How well cannabi- noid-based treatments hold up depends on how one defines suc- cess. The recommended dose of Marinol for appetite stimulation is 2.5mg twice daily. Studies prior to 2000 used this dose. In 1995, 2.5mg Marinol twice daily was compared to placebo to treat symp- toms of wasting in 139 HIV patients. Patients were randomly assigned to either the drug (88) or the placebo (51) group. When com- pared to the placebo group, the group receiving the Marinol report- ed substantial improvements over pre-study baseline in appetite, mood, and decreased nausea. Mean weight was stable in the Marinol group as compared to a small drop in weight for the placebo group. Over the course of the study, only 10% of the placebo group gained 2kg or more where as this was achieved by 22% of those in the Marinol group. These findings lead the authors to conclude that THC was “safe and effective” at alleviat- ing symptoms of AIDS wasting (18). A long term (12 month) trial of 2.5mg Marinol in late stage AIDS patients, which concluded THC was safe and effective in the long run, was published by the same group two years later. Again Marinol was associated with stable body weight and significantly improved appetite. Interestingly, the degree to which appetite improved over baseline was depen- dant on how long the patient had been on Marinol therapy such that scores during the first four months improved by 50-75% but went up to the 200% range there after (19). These studies help demonstrated something about the 2.5mg dose of Marinol. It is an effective appetite stimulating dose but does not
appear to consistently initiate weight gain, a fact that other researchers have used to claim that THC is ineffective when compared to other anti-wasting drugs. A 1997 study compared the suggested dose of Marinol to that of mege- strol acetate, the two doses togeth- er and a sub therapeutic dose of megestrol acetate and the suggested dose of Marinol together. Both groups using full doses of megestrol acetate gained an average of 6kg over the 12 week period. The group receiving Marinol alone lost an average of 2kg while the sub thera- peutic dose of megestrol acetate plus Marinol only lost 0.3kg. The difference between the four groups was found to be highly statistically significant. The lack of weight gain observed in the Marinol group lead the researches to conclude that THC was not an effective treat- ment compared to other available anti-wasting drugs (20).
More light as been shed on this controversy since 2000. Haney in 2002 reported that both Marinol and smoked cannabis standardized for THC content effectively increase food intake in a small study population of nine patients. Marinol appeared to produce a greater weight gain, however, smoked cannabis was rated higher for improved appetite and mood. Interestingly, Haney got these results using Marinol doses that were four to twelve times the rec- ommended dose for appetite stimu- lation (10mg, 20mg, 30mg), indi- cating that perhaps the recom- mended dose is conservatively small compared to what might be required for more severe conditions such as AIDS wasting (The stan- dardized cannabis doses used in this study were standard govern- ment issue joints of 1.8%, 2.8% and 3.9% THC.) (21). Three years later, Haney and colleagues, pub- lished more detailed findings con- cerning the use of smoked cannabis vs. Marinol in the treatment of AIDS wasting. Using the same
doses as Haney's earlier study, the effects of Marinol and smoked cannabis were compared in 15 HIV patients with signs of wasting and 15 without. For a few patients, the 30mg dose of Marinol was too intense, however all other doses of both Marinol and cannabis were well tolerated. Significant increases in caloric intake were associated with both cannabis and Marinol when compared to placebo for the group with signs of wasting but not those without (22). Clearly the appropriately anti-AIDS wasting dose of Marinol is as much as 8 times that currently recommended for full effect. Furthermore, it may only be effective at increasing weight in those who are already expressing evidence of wasting. This effect is comparable to that observed when cannabis with a low per cent THC is smoked for the same purpose.