____________________________________________________ Medical Marijuana and Other Cannabinoids
Cannabinoid Hyperemesis Syndrome Cannabinoid hyperemesis syndrome (CHS) is characterized by severe cyclic nausea and vomiting in chronic (usually heavy) cannabis users [170]. It is a relatively rare adverse effect, but increasing case reports have been noted with the liberaliza- tion of cannabis in several states [171]. Individuals with CHS experience temporary relief of symptoms with hot baths or showers, and compulsive bathing is often an identifying feature (differentiating the condition from other causes of cyclic vomit- ing) [172; 173]. Typically, patients begin with recurrent nausea and progress to intense, persistent vomiting with continued use of cannabis. The underlying pathogenesis of CHS is unclear, although several theories have been presented. One theory is that the enteric emetic effects of cannabis (e.g., decreased gastrointesti- nal motility) may promote emesis by over-riding the antiemetic effects mediated by the CNS [172]. Symptoms resolve with cessation of cannabis use; relapse to use often results in a recur- rence of the syndrome. Early recognition of CHS is essential to prevent complications related to severe volume depletion [173]. TREATMENT EFFICACY Neurologists in the 1970s began identifying two distinct patient groups self-medicating with cannabis for symptom alle- viation: wounded Vietnam War veterans with traumatic spinal injury and female patients with multiple sclerosis, migraine, or menstrual pain. Although these observations led to several small clinical trials supporting the claims of individual patients, regulatory hurdles in conducting clinical research resulted in relatively few efficacy studies [157]. Since 2000, there has been a significant increase in the quantity and quality of cannabis efficacy studies. For some clinical conditions, most of the published research involves oral cannabinoids, and there are questions over the extent this efficacy can be extrapolated to cannabis. Some reports indicate that patients benefiting from oral cannabi- noids are likely to benefit from smoked cannabis, but the reverse is not always true [165]. For example, inhaled cannabis trials for the management of nausea and vomiting are sparse. Although RCTs of dronabinol or nabilone predominate and have consistently shown efficacy, patients tend to prefer smoked over oral delivery due to the rapid alleviation of nausea and vomiting, ease of titration, and greater tolerability. Thus, for indications for which cannabis RCTs are few or absent, it seems reasonable to extrapolate non-cannabis cannabinoid efficacy to smoked cannabis. CHRONIC PAIN As noted, cannabis and other cannabinoids are seldom con- sidered first-choice therapeutic options but are used instead in patients for whom standard therapies are ineffective or intoler- able either as sole therapy or more typically as an add-on to the current regimen [2]. Cannabis has been safely co-administered
The severity of cannabis withdrawal, and whether it develops at all in strictly medical users, is unknown. With cessation of regular medical use, the pharmacokinetics and possibly pharmacodynamics of THC, such as slow elimination, may diminish withdrawal symptom manifestation into the subclini- cal level of severity [28]. Cannabis Addiction Roughly 9%, or 1 out of 11, who use recreational marijuana will develop an addiction syndrome; the figure increases to 17%, or 1 out of 6, who begin use in their early teens [19; 165]. This compares with lifetime prevalence rates of 32% for nicotine, 23% for heroin, 17% for cocaine, and 15% for alcohol [19; 166; 167]. Addiction risk among medical cannabis users is unknown. Data on cannabis addiction and risk factors come primarily from recreational users who began during adolescence or early adulthood and used high-potency cannabis with great frequency and intensity in the absence of medical supervision. Whether these data apply to the typically older adult patient using smaller doses of medical marijuana for symptom control is not known [168]. According to the Hartford Institute for Geriatric Nursing, little research on effective intervention for psychologic dependence on marijuana is available. Some guidance can be found in smoking cessation and self-help approaches. (https://hign.org/consultgeri/resources/protocols/ substance-misuse-and-alcohol-use-disorders. Last accessed November 21, 2023.) Level of Evidence : Expert Opinion/Consensus Statement The psychoactive effects and potential abuse liability of rec- reationally used cannabis are well known, but little is known of this potential with nabiximols spray (equal-ratio THC and CBD). A safety analysis using all published and unpublished nabiximols RCTs found that intoxication scores were low [166]. Euphoria was reported by only 2.2% of subjects, development of tolerance was not documented, abrupt cessation did not result in a withdrawal syndrome, and no cases of abuse or diver- sion were reported. An abuse liability study of nabiximols in experienced recreational cannabis smokers found some abuse potential at higher doses relative to placebo, but consistently lower abuse liability than equivalent doses of pure THC [166]. Although medical marijuana laws in some states have been anecdotally linked to increased recreational use among ado- lescents, a 2013 evaluation of the effects of these laws on adolescent marijuana use from 2003 through 2011 found that they had no measurable effect [169].
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