Neuro-Ophthalmology & Neuro-Otology
Third nerve palsy
Jul. 25, 2022
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Cannabis, which for much of the past century was relegated to the status of an oddity (at best) or a drug of abuse (at worst), has in recent years seen a resurgence in its public popularity and use. A number of studies show that a majority of Americans believe cannabis should be legalized, and its use has doubled in the last decade (21). Concordant to this groundswell of public opinion is the increasing public and medical perception of cannabis as a potential treatment for a variety of medical symptoms, including nausea, pain, and anxiety. AAN guidelines as well as stories in the popular media have raised patient perception of its possible utility in a variety of specific neurologic conditions as well. This coincides with increasing legalization of the drug for a variety of health conditions. Given the increasing availability and patient interest in the potential applications of cannabis, clinician understanding of the history, risks, pathophysiology, and available clinical data, both in animal and human studies, is essential to accurately educate patients and make informed decisions about whether its use could provide benefit for specific neurologic diseases.
• The use of cannabis for the treatment of neurologic disease dates back hundreds to thousands of years, with more recent restrictions placed within the last century.
• The human endocannabinoid system on which cannabis acts is composed of postsynaptic cannabinoid ligands that act presynaptically on endocannabinoid receptors, namely, CB1. This appears to function as a negative feedback system. Endocannabinoid receptors are found throughout the CNS and may serve a variety of functions.
• With regard to side effects, acute use of cannabis has been shown to cause anxiety and panic, impaired attention/memory/psychomotor performance, increased chance of psychosis in those already predisposed, and tachycardia. Long-term effects are less well studied, but there is evidence of cannabis dependence, bronchitis, increased risk of auto accidents, and the potential for mild withdrawal symptoms. There is no evidence cannabis use increases risk of cancer, leads to permanent psychiatric/cognitive deficits, or can result in overdose.
• Data from clinical trials, both animal and human, are extremely limited, owing in some part to the current legal restrictions on the drug.
• Multiple sclerosis has the most robust evidence for the efficacy of cannabis. Numerous large, randomized, and often double-blind European trials using the tetrahydrocannabinol (THC)/cannabidiol (CBD) combo drug nabiximols (ie, oral cannabis extract) have shown significant subjective improvement primarily in spasticity and pain, without changes in disability measures.
• Though basic science research suggests cannabis may suppress seizures in epilepsy, and some clinical trials suggest benefit in specific pediatric epilepsy syndromes, there remain insufficient clinical data to comment on its broader efficacy on epilepsy as a whole.
• The effect of cannabis on Parkinson disease is conflicting and poorly understood, both mechanistically and clinically. These patients are also at particular risk for a number of cannabis side effects (psychosis, fatigue, memory problems).
• Similarly, basic research on cannabis for the treatment of headaches is compelling, but despite a plethora of anecdotal reports, there are no convincing clinical trials proving its efficacy.
• There are insufficient data to comment on the effects of cannabis on other neurologic conditions.
The term “cannabis” is derived from the Greek kánnabis. The use of cannabis for neurologic disease can be traced at least as far back as 1500–3000 BC, in the writings of Chinese Emperor Shen-Nuang. Much of the early use of the drug was for treatment of headaches, with first documentation of its use for this purpose in 600 AD. Hildegard von Bingen, a 12th century European mystic, wrote “whoever has head pains may eat [cannabis] and the head pains may be reduced.” Dr. William O’ Shaughnessy is attributed with introducing medicinal cannabis to the West in the mid-1800s for uses including spasms in rabies and tetanus, cholera, and infantile convulsions. William Osler advocated its use for migraines in the early 1900s. Though widely accepted well into the first half of the 20th century, the decline of public and legal acceptance of cannabis in the United States came with the passage of the Marihuana Tax Act of 1937, which made cannabis significantly more expensive and began to shift the public perception of it to a drug of abuse. The chemical structure of THC, the primary psychoactive component of cannabis, was discovered in the late 1960s. However, the U.S. Comprehensive Drug Abuse Prevention and Control Act of 1970 made cannabis a Schedule I drug, legally defining it as a substance with no currently accepted medical usage and high potential for abuse. Though it remains illegal on a federal level, as of 2021, 36 states have legalized it for medical purposes and 18 have legalized it for recreational usage. International laws on the use of cannabis vary widely from country to country, ranging from total prohibition to legalization for recreational purposes.
The structure of the first endocannabinoid receptor, CB1, was discovered in 1990, marking the beginning of our understanding of the endogenous endocannabinoid system (30; 34; 06).
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