Pros, Cons and Options for Patients
By Paul Armentano
Senior Policy Analyst - NORML/NORML Foundation
Updated August 11, 2005
Research Assistance provided by Paul Varnado
Marinol1 (dronabinol) is the only US FDA-approved synthetic cannabinoid. It is often marketed as a legal pharmaceutical alternative to natural cannabis.
Marinol is manufactured as a gelatin capsule containing synthetic delta-9-tetrahydrocannabinol (THC) in sesame oil. It is taken orally and is available in 2.5mg, 5mg and/or 10mg dosages. Marinol may be prescribed for the treatment of cachexia (weight loss) in patients with AIDS and for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.
Despite FDA approval2, Marinol typically provides only limited relief to select patients, particularly when compared to natural cannabis and its cannabinoids. Marinol should remain a legal option for patients and physicians; however, federal and state laws should be amended to allow for those patients who are unresponsive to synthetic THC the ability to use natural cannabis and its cannabinoids as a medical therapy without fear of arrest and/or criminal prosecution. By prohibiting the possession and use of natural cannabis and its cannabinoids, patients are unnecessarily restricted to use a synthetic substitute that lacks much of the therapeutic efficacy of natural cannabis.
Chemical compounds in cannabis, known as cannabinoids, are responsible for its numerous therapeutic benefits. Scientists have identified 66 naturally occurring cannabinoids.3
The active ingredient in Marinol, synthetic delta-9-tetrahyrdocannabinol (THC), is an analogue of one such compound, THC. However, several other cannabinoids available in cannabis -- in addition to naturally occurring terpenoids (oils) and flavonoids (phenols) -- have also been clinically demonstrated to possess therapeutic utility. Many patients favor natural cannabis to Marinol because it includes these other therapeutically active cannabinoids.
For example, cannabidol (CBD) is a non-psychoactive cannabinoid that has been clinically demonstrated to have analgesic, antispasmodic, anxiolytic, antipsychotic, antinausea, and anti-rheumatoid arthritic properties.4
Animal and human studies have shown CBD to possess anti-convulsant properties, particularly in the treatment of epilepsy.5 Natural extracts of CBD, when administered in combination with THC, significantly reduce pain, spasticity and other symptoms in multiple sclerosis (MS) patients unresponsive to standard treatment medications.6
Clinical studies also demonstrate CBD to be neuroprotective against glutamate neurotoxicity7 (i.e. stroke), cerebral infarction8 (localized cell death in the brain), and ethanol-induced neurotoxicity,9 with CBD being more protective against glutamate neurotoxicity than either ascorbate (vitamin C) or alpha-tocopherol (vitamin E).10 Clinical trials have also shown CBD to possess anti-tumoral properties,11 inhibiting the growth of glioma (brain tumor) cells in a dose dependent manner and selectively inducing apoptosis (programmed cell death) in malignant cells.12
Additional cannabinoids possessing clinically demonstrated therapeutic properties include: cannabinol (anticonvulsant13 and anti-inflammatory14 activity); cannabichromine (anti-inflammatory15 and antidepressant16 activity); and cannabigerol (anti-tumoral17 and analgesic18 activity). Natural cannabis' essential oil components (terpenoids) exhibit anti-inflammatory properties19 and its flavonoids possess antioxidant activity.20 Emerging clinical evidence indicates that cannabinoids may slow disease progression21 in certain autoimmune and neurologic diseases, including multiple sclerosis22 (MS), Amyotrophic Lateral Sclerosis23 (Lou Gehrig's disease) and Huntington's Disease.24
Clinical data indicate that the synergism of these compounds is likely more efficacious25 than the administration of synthetic THC alone.26 For example, McPartland and Russo write: "Good evidence shows that secondary compounds in cannabis may enhance beneficial effects of THC. Other cannabinoid and non-cannabinoid compounds in herbal cannabis ... may reduce THC-induced anxiety, cholinergic deficits, and immunosuppression. Cannabis terpenoids and flavonoids may also increase cerebral blood flow, enhance cortical activity, kill respiratory pathogens, and provide anti-inflammatory activity."27 In an in vitro model of epilepsy, natural cannabis extracts performed better than THC alone.28 In human trials, patients suffering from multiple sclerosis experienced greater symptomatic relief from sublingual natural cannabis extracts than from the administration of oral THC.29 In 2005, Health Canada approved the oral spray Sativex30 -- which contains precise ratios of the natural cannabinoid extracts THC and CBD, among other compounds -- for prescription use for MS-related symptoms.31
Patients prescribed Marinol frequently report that its psychoactive effects are far greater than those of natural cannabis. Marinol's adverse effects include: feeling "high," drowsiness, dizziness, confusion, anxiety, changes in mood, muddled thinking, perceptual difficulties, coordination impairment, irritability, and depression.32 These psychoactive effects may last four to six hours.33 About one-third of patients prescribed Marinol report experiencing one or some of these adverse effects.34
Marinol’s oral route of administration is responsible, in part, for its heightened psychoactivity compared to inhaled cannabis. Once swallowed, Marinol passes from the stomach to the small intestine before being absorbed into the bloodstream. Following absorption, Marinol passes through the liver where a significant proportion of the drug is metabolized into other chemicals.35 One of these chemicals, 11-hydroxy-THC, may be four to five times more potent than natural THC,36 and is produced in greater quantities.37 Thus, patients administered Marinol experience the psychoactive effects of both THC and 11-hydroxy-THC, greatly increasing the likelihood that they will suffer from an adverse psychological reaction. By comparison, only minute quantities of 11-hydroxy-THC are produced when cannabis is inhaled.38 Moreover, Marinol lacks the compound cannabidiol, which possesses anxiolytic activity and likely modifies and/or diminishes much of THC's psychoactivity in natural cannabis.39