Quote: “I am in no form or fashion advocating the smoking of cannabis, a practice that is associated with numerous well documented severe health risks. Neither do I support its legalization. However the effects of cannabis are the result of the body, and the brain in particular, possessing its own endogenous cannabinoid system. We are seeking to understand this system, how its works, how it can be modified and how targeted drug delivery systems can be developed that maximize clinical benefits and minimize unwanted side effects.”
The Cannabis sativa plant has had a long, colourful and often controversial association with mankind. Originally cultivated to make hemp, a soft and durable fibre that was used extensively in the pre-industrial era for the production of rope, textiles and paper, it is also one of the oldest herbal remedies known to man, with texts from ancient China and India detailing its use as a treatment for a variety of illnesses. Even Queen Victoria of Britain is reported to have used it as a preparation for the treatment of menstrual cramps. Despite this wide variety of uses and its extensive commercial production (up to today over 40,000 hectares of hemp are under cultivation worldwide) cannabis is best known for its psychoactive properties and its association with recreational drug use (marijuana).
The Caribbean region, rightly or wrongly, has anecdotally been associated with the use of cannabis for such hedonistic purposes. The stereotypical image of a Rastafarian resplendent with ‘joint,’ as often personified by Bob Marley, is an iconic image of supposed Caribbean life. Those of us who live and work in the region know this demographic grouping actually represents the minority and best estimates of regular cannabis use are less than ten per cent.
The smoking of cannabis can produce a number of effects on the human body including disordered perception relating to sights, sounds, touch and even time, short-term memory loss and disruption of learning, a sense of mild euphoria and a feeling of tranquillity, anxiety, loss of motor skills, increased heart rate, pain relief, dry throat and mouth. This list is by no means exhaustive, and for decades, scientists have been intrigued by how this plant could have such a wide and varied response on so many different physiological systems. Research over the last 40 years has begun to answer this question and in particular, discoveries since 1990 have exponentially increased our knowledge and understanding of cannabis, how it works and what effects it has on the human body.
This new era of understanding began in 1964 when the primary active ingredient of cannabis, delta-9-tetrahydrocannabinol (THC) was identified. Advances in cannabinoid physiology proceeded slowly over the next two decades but of note during this period was the contribution made by two Caribbean scientists, Manley West and Albert Lockhart. West and Lockhart started their journey in cannabinoid research when they noted (i) a reduction in glaucoma among Rastafarians who traditionally used cannabis and (ii) persons from rural communities who used eyewash purportedly derived from cannabis claimed improved eyesight. This triggered ten years of pioneering research that culminated with the development and patent of a drug, Canasol, for the treatment for glaucoma.
In 1990, cannabinoid research really took off when the first THC receptor in the brain was discovered. Very soon afterwards another receptor was identified and scientists believe there are at least two more cannabinoid receptors still waiting to be fully characterized. Perhaps more fascinating though was the discovery two years later that the brain produces neurotransmitters itself that do the same thing as THC. In other words the brain produces its own ‘cannabis-like substances’. The most common and first discovered was named anandamide, derived from the Sanskrit word ananda meaning bliss. These naturally occurring substances produced by the body are called endocannabinoids. Together with their receptors they form the framework of a complex endocannabinoid signalling system which is found in many regions within the central nervous system and in a number of important peripheral tissues.
Given the widespread and complex nature of this cannabinoid system it is not surprising that it has been implicated in a number of physiological processes including learning and memory, regulation of appetite, immune function, regulation of pain and activation of neuroprotective pathways. Knowledge of these processes and how they can be manipulated is important as they offer novel forms of intervention in diverse clinical scenarios. At this point it should again be noted that researchers do not advocate the imbibing of cannabis, via smoking or otherwise, as an effective clinical intervention. What is being considered though, is targeted drug delivery systems through the development of specific compounds that minimize unwanted side effects and maximize clinical benefits. Some of the more interesting and relevant findings to date are detailed below.
Modulation of Pain
Learning and Memory
Immunological Function and multiple sclerosis
Endocannabinoids and neuroprotection
In conclusion, our understanding of cannabinoids has dramatically increased within the past 20 years. This understanding has shed new light on the numerous processes in which endocannabinoids are involved and offered new vistas for modulation of these same processes. Despite the tremendous advances that have been made, successful interventions have yet to be fully elucidated. This is the ‘holy grail’ of cannabinoid research, the ability to develop compounds that disentangle the benefits of cannabinoids from their pitfalls and psychotropic side effects. Until this is done, the full potential of harnessing this system remains locked away, though results to date provide ample incentive for those currently working in the field.
-Dr. Farid F. Youssef is a lecturer, Department of Pre-Clinical Sciences, Faculty of Medical Sciences, UWI, St. Augustine Campus.