Marijuana or cannabis extracted from cannabis plant possesses about 483 known compounds including at least 65 cannabinoids, most active THC (Tetrahydrocannabinol). The drug causes “high” or “stoned” feeling, euphoria and change in perception, that are used, mostly smoked for. But the drug has many other effects, or side-effects such as an increase in appetite, impairing cognition (attention, concentration, memory, thinking, learning, planning, etc.), dry mouth, impaired motor skills, red eyes, anxiety or its exacerbation and even paranoia and psychosis in susceptible individuals. Globally an average of 4% of the world population between the ages of 15 and 65 use marijuana. In 2015, 43% of Americans had used cannabis, which increased to 51% in 2016. All these data makes Marijuana, the most commonly used illegal drug both in the world and the United States. (1-2)
Marijuana or Cannabis: Benefits Vs. Harms
Marijuana or Cannabis that is considered by lay people and lawmakers and some physicians to have potential medical benefits, and medical marijuana has been legislated in many parts of the world, is not as beneficial that is harmful. A recent meta-analysis found that cannabinoids that were originally justified in medical use for treatment of cancer chemotherapy-related nausea and vomiting, or in the treatment of pains and spasticity, showed inconclusive benefits for many of these indications such as improvement of appetite and weight, reduction in tic severity, and improvement of mood or sleep in such patients. On the flip side, cannabinoids and cannabis have acute and long-term adverse effects. In randomized controlled trials, cannabinoids increase the risk of total adverse events, serious adverse events, and dropout due to adverse events. Cannabis impairs cognition, and driving after cannabis use is associated with an increased risk of traffic accidents, including fatal accidents. Long-term cannabis use may lead to dependence, respiratory conditions, psychosis. Cannabis use during pregnancy may compromise certain pregnancy outcomes such as fetal growth, and use during adolescence may compromise neurodevelopment, social adjustment, and vocational success. (3-17)
Data from the Global Burden of Disease Study 2010 suggested that, during 2010, an estimated 13.1 million persons were dependent on cannabis; peaked in the 20- to 24-year age group, and was nearly twice as high in males as in females. Cannabis dependence was associated with 2,057,000 years of life lived with disability and the same number of disability-adjusted life-years. In Canada, these statistics were estimated to be 10,533 years of life lost due to premature mortality, 55,813 years of life lost due to disability, 66,346 disability-adjusted life-years, and 287 deaths in 2012. (3-6) Cannabis use has long been suggested to adversely affect cognition, and a recent systematic review concluded that verbal learning and memory and attention are functions that are most consistently impaired by acute and chronic cannabis use. (7) Psychomotor impairment occurs most obviously during acute intoxication but may be detected in chronic users, as well. The neuropsychological deficits probably arise from impairments that have been identified in hippocampal, prefrontal, subcortical, and other brain networks that subserve cognition. (8)
A systematic review and meta-analysis of 9 studies covering 49,411 individuals showed that driving after cannabis use was associated with a doubled risk of motor vehicle accidents In studies that assessed cannabis use combined with alcohol, the risk estimate was higher with combined use relative to cannabis use alone, suggesting additive or synergistic adverse psychomotor effects. Also, laboratory and driving simulation studies have consistently shown that cannabis dose-dependently impairs psychomotor skills and that cannabis use is a specific risk factor for traffic accidents. (7-10)
Since cannabis users inhale more smoke and inhale more deeply than tobacco users, they also have a 5-fold increase in carboxyhemoglobin concentration. Smoking 1 cannabis cigarette is associated with the airflow obstruction resulting from smoking 2.5–5.0 cigarettes. Cannabis smoking is associated with respiratory risks similar to those associated with cigarette smoking. (11) Constituents of cannabis cross the placental barrier, are found in breast milk, and can therefore affect pregnancy outcomes and neurodevelopment. Adverse outcomes associated with cannabis exposure during pregnancy include fetal growth restriction, preterm birth, and stillbirth. (12-13)
Impairments in several cognitive domains are not just limited during the use of cannabis but even after its discontinuation. These adverse effects are more severe in childhood and adolescence whose brains are still in the different stages of development. These neurodevelopmental delay effects could continue even into the second decade of life and beyond. These adverse impact on cognition could conceivably compromise social adjustment and vocational success. (14-16) More than an acute and simple cognitive impairment among the cannabis users, a long-adverse effect of risk of marijuana use has been the predisposition to psychosis or even schizophrenia in susceptible individuals, or even through impacting on the fetus while smoked by the pregnant mothers. Recent longitudinal studies suggest that there is up to a 40% greater risk of psychosis in individuals who have ever used cannabis. There is also evidence of a dose-effect relationship between cannabis use and schizophrenia risk. (18) Cannabis usage in adolescence has additionally been proposed to induce first episode psychosis at a younger age, with some researchers suggesting that cannabis usage can induce the onset of psychosis up to 2.7 years earlier than in those who develop psychosis without a history of cannabis usage. (19)
What about now: Medicalization and Legalization of Marijuana:
The story of the recent medicalization of marijuana starts with the earlier legalization or minor restrictions on the use and distribution or decriminalization of this drug. As of 2017, Australia, Bangladesh, Canada, Chile, Colombia, Costa Rica, the Czech Republic, Germany, India, Jamaica, Mexico, the Netherlands, Portugal, South Africa, Spain, Uruguay, and some U.S. jurisdictions have the least restrictive cannabis laws. But many countries in the world still consider this drug as illicit and have the strictest rules against the use and its distribution such as China, France, Indonesia, Japan, Malaysia, Nigeria, Norway, the Philippines, Poland, Saudi Arabia, Singapore, South Korea, Thailand, Turkey, Ukraine, the United Arab Emirates and Vietnam. (20)
While cannabis plant contains at least 113 active cannabinoids, mainly THC and CBD (Cannabidiol), the synthetic or medical cannabis approved for medical use in some countries such as US and Canada, are made of these two compounds. THC that is the most psychoactive compound of cannabis or marijuana and the reason it is smoked or used for elation, relaxation and good feeling has been attempted in the synthetic cannabis to be reduced in amount, but increase in the amount of CBD that is not psychoactive, but in fact antagonist of THC. In fact CBD has a very low affinity for cannabinoid or CB receptors, but acts as an indirect antagonist the these receptors. While CBD may have a down-regulating impact on the cognitive impairment effect of THC or street marijuana, it accounts for up to 40% of the plant’s extract and also has some potentiating effect on THC through increasing CB1 receptor density and via inhibition of cytochrome enzymes degrading the product. (21-22)
The three common market brand names of medical marijuana or cannabis are Nabilone (Cesamet); Dronabinol (Marinol) and Nabiximols (Sativex). Nabilone taken orally, in fact mimics more THC, the main ingredient of cannabis or marijuana, although the users have reported to have more CBD effect than THC, so less “high” effect on the mind. It has mostly anti-emetic effect for treatment of nausea and vomiting in treating cancer patients and some probable adjunct analgesic effects on some neurogenic pains. Dronabinol is another synthetic THC more used for the treatment of anorexia associated with AIDS-related weight loss and still holds some potential for dependence. Nabiximols that is synthesized and marketed as a mouth spray contains almost equal amount of THC (2.7 mg) and CBD (2.5 mg) and is used for alleviation of neuropathic pains and spasticity. (23-24)
In summary, the legalization of marijuana is different than medicalization of this drug. The legalization of marijuana or weed that is currently smoked and illegal in many parts of the world, by some countries such as Canada and some states in US, will decriminalize a drug that has been for many years illegal for its toxic recreational effect. In brief any drug or agent tempering with our brain functions is unhealthy and non-medical, even drinking alcohol, though this has been customarily approved by humans from the time of antiquity, despite its addiction and toxic properties. But still the use of alcohol in many countries, even the western world is prohibited and illegal in under-age groups who are still in the developing brain stage and could have more harmful impact of drinking prematurely.
But legalization of marijuana, while it could be voluntarily used in the adult age groups, despite the knowledge of its toxic effect, for example on the cognitive functions, how it could be curbed for the use in children and adolescents. Although alcohol in many countries has an age limit use, above 18 or 19 and in some US states even 21, the brain is still in developmental stage until age 25-26 and could be affected negatively by it and other psychoactive drugs until mid-20’s more than the adult age, impacting its normal development. The same is true for other psychoactive drugs such as marijuana or cannabis, and more so due to its path of delivery to the brain through smoking that is much faster than oral delivery path of some drugs like alcohol.
Medicalization of marijuana if it is for the treatment of nausea, vomiting, increasing appetite and in pains and for medically and terminally ill patients population, could be justified medically as long as being effective, not addictive and not toxic. But universal medicalization of marijuana or cannabis with opening numerous clinics, selling and distributing them, like what is happening in Canada, for many other medical indications, such as psychiatric conditions, like depression and anxiety is a true foolishness. First of all as detailed above, the current synthetic cannabis does not contain more CBD to have such effect, but more or equal amount of THC with its psychoactive or “high” effect that many old or current marijuana smokers are looking for the same.
The main effect of marijuana or cannabis on the brain is through interaction with cannabinoid receptors, creating some elation or “high” or relaxation, and not through the monoamine receptors such as serotonin or norepinephrine that are in control of our mood. Regarding the indication of medical marijuana for the treatment of pains, CB receptors are not much involved as opioid receptors and synthetic products affecting them such as morphine, codeine and their derivatives, that have been long in medical use, improportionately and inappropriately so to have made the narcotic prescription use more frequent than all illicit narcotic use in the western world. (25) Therefore to do the same in medicalization of cannabis universally would be spreading non-medical and illegal use of another narcotic, causing more addiction, and neurologic and psychiatric toxic effects, and probable more so on the under-age population.
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