Medical Marijuana

2015

In addition to the adverse consequences on health previously discussed, cannabis may also have beneficial effects for a number of medical conditions. Oral THC (dronabinol) has been approved by the U.S. Food and Drug Administration for use as an appetite- and food-intake stimulant in patients with AIDS wasting syndrome and as an antinausea and antivomiting agent in cancer patients receiving chemotherapy. In 1999, the Institute of Medicine and the National Institutes of Health acknowledged the importance of initiating additional scientific study of the risks and benefits of cannabis use and, in particular, smoked marijuana for specific medical conditions. The interest in the benefits of smoked marijuana in contrast to oral THC arises primarily from differences in the pharmacokinetics of these two routes of administration. Through the oral route, THC absorption is slow and variable, and therefore clinical effects have a slower onset and longer duration than smoked marijuana. In addition, smoked marijuana not only delivers delta-9-THC, but other compounds (e.g., delta-8-THC and cannabidiol) are absorbed that may have direct or interactive effects of therapeutic interest.

Illnesses Involving Appetite, Food Intake, and Nausea Problems

Acute cannabis use can increase appetite and food intake. Single- and multiple-dose studies with marijuana and oral THC reliably show increases in food intake and food choice, since cannabis intoxication appears to result in frequent snacking and increased choice of sweet solid foods. Interestingly, recent studies also show that abrupt discontinuation of oral THC or marijuana can result in decreased appetite and food intake, as well as concomitant weight loss during the first few days of withdrawal.

Cannabis’s ability to facilitate appetite and food consumption prompted consideration of use of oral THC and smoked marijuana in clinical populations such as patients with AIDS wasting syndrome. Controlled case studies suggest some benefit of cannabis and THC for increasing appetite and weight gain in patients with AIDS wasting syndrome, but mixed results best characterize this literature.

Cancer patients’ reports of the efficacy of smoked marijuana for relief from the nausea and vomiting associated with chemotherapy have stimulated study of such effects using oral THC and smoked marijuana. Placebo-controlled studies demonstrated the efficacy of oral THC (dronabinol) for this purpose, although other antiemetic drugs may work at least as well and are accompanied by fewer side effects. The efficacy of smoked marijuana in this clinical population has received little systematic study. Case reports commonly indicate the benefits of smoked marijuana, but the only controlled study conducted thus far did not demonstrate it to be superior to oral THC.

As mentioned earlier, the problem with absorption of THC when taken orally in contrast to the efficiency of THC delivery with smoked marijuana has triggered the call for more systematic study of smoked marijuana as an optimal method for achieving antiemetic and appetite effects in these clinical populations. However, the potential adverse effects of smoked marijuana on immune system function (reviewed previously) must be carefully considered as a contraindication for the use of smoked marijuana with immune-compromised clinical populations. Controlled research comparing the efficacy of oral THC and smoked marijuana is needed to determine whether cannabis should be considered a treatment of choice for severe problems with nausea and appetite in chronically ill populations.

Analgesia

The discovery of the endogenous cannabinoid system has rekindled interest in the use of cannabis for the treatment of pain. Elevated levels of cannabinoid receptors are located in areas of the brain that modulate no-ciception and can also be found in peripheral tissue. Recent research in nonhumans using animal models of pain indicate that cannabinoid agonists clearly exert analgesic effects in both the CNS and the periphery. The mechanisms for these analgesic effects differ from that of the opioids; hence, the potential use of cannabinoids as an adjunct or alternative treatment for acute or chronic pain has received increased attention.

The evidence for analgesic effects of cannabis in humans is less clear. Historically, the few studies of the effects of cannabis, THC, or other cannabinoid analogues on acute pain (i.e., laboratory induced or surgical) have not produced impressive results. Greenwald and Stitzer reported significant dose-dependent antinociceptive effects of smoked marijuana using a radiant-heat pain stimulus. However, the effects on pain reduction were not clinically robust and lasted less than one hour. Unfortunately, most of the research in this area has not been methodologically strong, making interpretation of findings difficult.

Early research on chronic pain demonstrated that oral THC and a nitrogen analogue produced analgesia similar to codeine, but side effects (sedation and depersonalization) were significant. To date the most evidence for the efficacy of smoked marijuana for pain reduction in clinical populations experiencing chronic pain comes from case reports and survey studies. Patients have reported relief from cancer-related chronic pain, pain related to neurological disease, muscle spasticity, and headaches as well as phantom limb pain. Many of these patients cite the superiority of smoked marijuana when compared to other treatments they have tried. Marijuana’s positive effects on nausea and appetite make it particularly attractive for chronic-pain patients who also experience problems in these areas (e.g., cancer chemotherapy or AIDS patients). Moreover, the “positive” effect of cannabis on mood may further add to its desirability among patients with these types of chronic debilitating illnesses.

Again, the potential differences in the effects of delivering THC and the other compounds found in cannabis through smoking compared with oral administration are reason enough to pursue additional study of smoked marijuana as an analgesic agent. Controlled studies are needed to (1) compare smoked cannabis with oral THC, (2) compare cannabis with other analgesics, and (3) examine the effects of combinations of cannabis and other analgesics (e.g., opioids). Of note, there is reason to hope that additional basic research on the analgesic effects of cannabinoids might result in the development of efficacious agents that do not produce the other problematic effects of THC such as sedation, memory problems, and intoxication.

Other Medical Indications

Spasticity Associated with Movement Disorders

Case studies have suggested that cannabis might help alleviate tremors, spasms, or loss of coordination associated with multiple sclerosis or other neurological disorders such as spinal cord injury. Controlled studies have not been conducted. Uncontrolled trials of oral THC have produced some evidence for a reduction in spasticity in patients with multiple sclerosis and spinal cord injury, but the effect has not been uniform and multiple side effects including loss of impaired posture and balance have been reported. Conclusions regarding the efficacy of cannabis and other cannabinoids for the treatment of muscle spasticity await data from controlled studies.

Glaucoma

Both smoked marijuana and oral THC can reduce intraocular pressure that contributes to glaucoma and its progression. Nonetheless, cannabis use is no longer a good choice for treatment of this disease. THC clearly reduces intraocular pressure, but this effect is transient and thus requires chronic, high doses multiple times per day to achieve the desired therapeutic response. Although not the case 10 to 20 years ago, alternative local treatments are now available which require less frequent dosing and have fewer adverse side effects than cannabis. Hence, cannabis should no longer be considered a treatment of choice for glaucoma.

The current literature on medical indications for cannabis includes primarily uncontrolled case studies or open clinical trials with only a handful of controlled studies of oral THC conducted, mostly in the 1970s. Nonetheless, a number of medical indications appear to have enough support to warrant additional investigation. Much more data on the efficacy of smoked marijuana and oral THC for various medical conditions will soon become available, as the NIH and other funding sources (e.g., Center for Medicinal Cannabis Research, UCSD, San Diego, CA) have initiated focused efforts to stimulate research in this area.

Selections from the book: “Handbook of the Medical Consequences of Alcohol and Drug Abuse” (2004)