cannabis THC

Credit: Pixabay.

Delta9-Tetrahydrocannabinol, or THC for short, is the active substance found in marijuana. It is responsible for its psychoactive effects. THC binds to cannabinoid receptors found in certain areas of the brain associated with cognition, memory, pleasure, coordination and time perception, producing a euphoric high in the process.

THC is naturally found in the resin produced by glands present in Cannabis sativa and Cannabis indicaBesides THC, there are actually many other cannabinoids present in the resin, possibly more than a hundred.

What are cannabinoids

2000px-Tetrahydrocannabinol

The THC molecule. Credit: Wikimedia Commons

THC was first isolated by Israeli chemist Raphael Mecholaum in 1964. Mechlaum synthesized THC from Lebanese hashish and his groundbreaking research opened the flood gates for research on both cannabinoids and endocannabinoids.

Cannabinoids act on central nervous system by imitating endocannabinoids, molecules which occur naturally in the human body. Not all, of them, however, are nearly as potent as THC. In fact, most of them aren’t psychoactive at all. For instance, Cannabidiol  (CBD) — another cannabinoid and possibly the 2nd most famous one after THC — is not only nonpsychoactive, it actually blocks the high from THC. Many medical marijuana proponents and enthusiast claim CBD is actually responsible for the positive medical effects of marijuana but, like most things related to marijuana, the science isn’t out yet.

Other important cannabinoids worth mentioning are:

  • Cannabigerol (CBG). This is essentially the stem cell of all cannabinoids. It is the precursor to THC, CBD, CBC and the rest. CBG is nonpsychoactive but it can turn into THC and THCV, the two molecules that will get you high. According to a 2011 study, CBG is a COX-2 inhibitor which acts by the same mechanism that aspirin, ibuprofen and other NSAIDs use to combat inflammation
  • Cannabichromene (CBC). Most strains contain CBC albeit in small amounts. According to a University of Mississippi study, CBC has antidepressant-like effects. CBC is also a potent anti-inflammatory substance, according to another study. 
  • Cannabinol (CBN). This is actually oxidized THC. It won’t get you high like THC, however, it’s a very powerful sedative which shows promise against insomnia and nerve pain, according to a study. Some marijuana users who are aware of the sedative effects of CBN will intentionally leave weed buds exposed out in the open to produce more CBN and self-medicate. Don’t try this at home.
  • Tetrahydrocannabivarin (THCV). As the name implies, THCV is a cannabinoid very similar to THC. But although the two molecules might look the same, they’re not exactly so. Like THC, THCV is psychoactive — even more so, some claim since it produces a euphoric high that is often described as psychedelic. One huge difference between THC and THCV is that the former provokes an appetite, the famous munchies, while the latter suppresses it.

A question marijuana-curious scientists have always pondered is why cannabinoids exist in the first place. Cannabinoids are secondary metabolites, meaning they’re substances that the plant produces which have no primary purpose in its development, whether it’s reproduction, photosynthesis or growth. Nature isn’t ‘stupid’ though. Seeing how any secondary metabolites have specific negative impacts on other organisms such as herbivores and pathogens, many scientists claim these have a protective value, like a sort of immune system.  Other famous secondary metabolites include nicotine and cocaine.

THC side effects

After the THC molecule binds to cannabinoid receptors, the interaction stimulates cells in the brain to release dopamine, the ‘feel good’ neurotransmitter responsible for euphoria. In doing so, THC also interferes with how information is being processed in the hippocampus, a horseshoe-shaped brain area that is responsible for the storage and retrieval of memories.

It’s worth keeping in mind that the way marijuana is taken determines the onset of effects. If smoked as a joint or inhaled through a bong or vaporizer, the effects of THC can be felt usually within a few minutes, sometimes a couple of seconds. If ingested with food, usually baked goods like brownies or muffins, the effects last longer, about 30 to 60 minutes or so.

Once the effects of marijuana set in, the user’s heart rate will jump by 20 to 50 beats/min, eye blood vessels expand lending blood-shot eyes and the bronchial passages open up. THC may also induce hallucinations, delusions, anxiety, and, in some cases, paranoia. The effects last on average about two hours but impaired motor control may persist after the high wore off.

Other short-term effects of THC include:

  • relaxation;
  • dry mouth;
  • altered perception of time;
  • hunger/munchies;
  • energy but also drowsiness;
  • memory impairment;
  • sedation/pain relief;

It’s important to note that the short-term effects of THC vary wildly from strain to strain according to potency. Because little research has been done on pure form THC, many of the supposed effects may be due to other cannabinoids. Terpenes, which are compounds that produce flavor and fragrance in plants, may also be involved. Effects will also vary from person to person according to body chemistry and mood. For instance, some people will become very anxious after ingesting THC while others will feel more relaxed or elated.

THC: from reefer madness to a drug beloved by many

Still from the movie Reefer Madness.

Still from the movie Reefer Madness.

Marijuana is the most commonly used illicit drug used around the world, though many states and nations have legalized or are in the process of doing so in the past decade. Since the first statewide medical marijuana laws went into effect in California in 1996, the number of Americans with legal access to the drug has steadily grown. Twenty states and the District of Columbia now permit the sale of various forms of marijuana for medical purposes.

The speed with which Americans are now considering legalizing marijuana has taken everyone by surprise considering its history of prohibition.

The first attempt at federal regulation of marijuana came in 1906, with the passage of the Pure Food and Drug Act. According to the act, companies were required to clearly label certain substances, including cannabis, on their medicine so customers can avoid it. Then, between 1914 and 1925, after an extremely unsuccessful attempt at prohibiting alcohol, temperance campaigners turned to opiates, cocaine, and marijuana. During this time,  twenty-six states passed laws prohibiting the plant with little debate and virtually no resistance from behalf of the public. That’s not all that surprising considering smoking cannabis was largely a habit of immigrants and the lower class back then.

Journalists, politicians, police, and the middle-class were not at all familiar with cannabis and this fact was exploited by some groups who were bent on turning the drug into a vessel of everyone’s greatest fears: addicting, personality-destroying, violence-causing.

“How many murders, suicides, robberies, criminal assaults, holdups, burglaries and deeds of maniacal insanity it causes each year can only be conjectured,” wrote Harry J. Anslinger in a 1937 article in American Magazine titled “Marijuana, Assassin of Youth.” Aslinger was a former assistant commissioner of the Prohibition Bureau who headed the U.S. Treasury Department’s Narcotics Bureau from 1930 to 1962 and one of the most vocal marijuana prohibitionists. In the same year, the Marijuana Tax Act, which regulated the drug by requiring dealers to pay a transfer tax, passed in the House. The rule effectively banned marijuana use and sales. Also in 1937, the now famous propaganda scare movie Reefer Madness appeared.

Steadily but surely, marijuana was demonized in the eyes of the public by journalists and politicians who had no patience for distinction among narcotics. Heroin, cocaine, and marijuana were all ‘dope’. In the 1970s, the Marijuana Tax Act was replaced with the Controlled Substances Act which established Schedules for ranking substances according to their dangerousness and potential for addiction. Cannabis was placed in the most restrictive category, Schedule I, supposedly as a place holder while then President Nixon commissioned a report to give a final recommendation. Alas, it has remained a Schedule I drug ever since despite a 5000-year history as a therapeutic agent across many cultures.

THC medical risks

Teenagers who use THC run at risk of affecting their brain development. Heavy marijuana users can trigger anatomical changes in the brain that affects memory among other things. Credit: Pixabay.

Teenagers who use THC run at risk of affecting their brain development. Heavy marijuana users can trigger anatomical changes in the brain that affects memory among other things. Credit: Pixabay.

Today, laws and public tolerance for the drug are moving in the direction of the nineteenth and early twentieth centuries, before the first attempts at federal regulation. At the same time, there are many things about the science of marijuana that are as unclear as they were a century ago.

For one, marijuana does not make the youth homicidal or hell-bent on raping innocent school girls. That’s something everyone is fortunately (or hopefully) aware is not true.

However, there seems to be a reverse wave of positive propaganda in favor of marijuana. Social media abounds with claims of marijuana being a miracle medicine for anything from a bad toothache to, of course, cancer.

The truth is, we know very little because marijuana in the United States is still illegal at the federal level so any researcher has to go through numerous loopholes, including the DEA, to get the plant for study. Remarkably, even though pot is used by millions of Americans and you can find it almost everywhere to buy off the book, there is only one single supplier of marijuana in the United States for research purposes, the University of Mississippi. As such, progress is very slow but there are still some things we know about the risks of THC.

Because THC impairs motor control, users shouldn’t drive. According to the National Highway Traffic Safety Administration, cannabis is the second-most common psychoactive substance found in drivers’ blood after alcohol.

According to a study which followed 1,037 New Zealanders from birth to middle age, marijuana doesn’t seem to cause physical health problems, with one notable exception: the gums. Results suggest those who used marijuana over the last 20 years showed an increase of periodontal disease compared to those who didn’t, starting from age 26. Marijuana smokers did not differ from non-users on any other health measure.

There are some consequences for cognition and brain health related to smoking marijuana, however. Teenagers and youngsters who smoked marijuana daily (or several times a week) for three years or more performed poorly on memory tasks and showed abnormal changes in their brain structure, according to a Northwestern Medicine study.

According to researchers at the National Institute on Drug Abuse in Bethesda, marijuana users who have abused the drug (who had smoked a median of about five joints a day, 5 days a week, for 10 years) showed damage in the brain’s pleasure center.  Some marijuana abusers also seem to react to anxiety-inducing stimuli similarly to people diagnosed with anxiety disorders. And one University of Warwick study found a link between cannabis use and an increased occurrence of mania symptoms or manic episodes.

A 2016 study followed the effects of highly potent strains with high Δ9-tetrahydrocannabinol content. It found heavy users showed anatomical alterations in a region of the brain called the corpus callosum, which connects the two cerebral hemispheres. The study set out to investigate whether there was any association between heavy use of potent strains and the onset of psychosis. No such association was found.

Smoking marijuana can also cause bronchitis which can be avoided by using alternative ingesting methods like edibles or vaping.

study from March 2016 found a link between poorer verbal cognitive function and consistent cannabis use. For every five years of cannabis use, participants couldn’t remember a word for a 15-word list. The sample size was rather small so the findings might be rather inconclusive.

There is no evidence that suggests using cannabis can cause cancer. That being said, smoking anything, whether it’s tobacco, marijuana or broccoli is bad for your health and should be avoided as much as possible.

THC medical benefits

Many people swear that cannabis oil can treat and even cure cancer but there is no scientific evidence that this is so yet. Credit: Wikimedia Commons.

Many people swear that cannabis oil can treat and even cure cancer but there is no scientific evidence that this is so yet. Credit: Wikimedia Commons.

According to Dr. Sanjay Gupta, only 6% of marijuana research studies the benefits out of nearly 20,000 recent papers (post 1930’s/1940’s). As such, research into the medical benefits of marijuana is still rather in an early stage with much to learn about both the good and bad things to come out of long-term use.

“It doesn’t have a high potential for abuse, and there are very legitimate medical applications. In fact, sometimes marijuana is the only thing that works,” he wrote. “We have been terribly and systematically misled for nearly 70 years in the United States, and I apologize for my own role in that.” (Gupta is a converted pro-marijuana physician)

In 2014, a study showed that inhaled cannabis can significantly mitigate Parkinson’s symptoms, and another one also showed some promise in easing pain and fighting depression.

Scientists at the Salk Institute labs in San Diego have published preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in cannabis can remove amyloid beta, the toxic protein most commonly associated with Alzheimer’s disease. Researchers from the same Salk Institute found evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer’s but their study only involves neurons grown in a dish in the lab.

Researchers from the Multidisciplinary Association for Psychedelic Studies (MAPS).found that people with PTSD had lower levels of anandamide, an endogenous cannabinoid compound, compared to those who did not show signs of PTSD.

In 2015, Dalhousie University researchers found marijuana relieves pain and repairs arthritic joints thanks to the pain-detecting nerves that are filled with cannabinoid receptors. According to the researchers, the cannabinoids control the pain signal that fires from the joint to the brain. Elsewhere, British researchers at the Royal National Hospital for Rheumatic Disease concluded cannabinoids provide a statistically significant improvement in pain at movement and rest but also improves the quality of sleep.

THC and CBD-based medications seem to have an effect in treating various afflictions associated with multiple sclerosis like muscle spasms, inflammation, gastrointestinal issues, mood issues, and pain.

Yale University researchers found cannabis causes the brain to produce a different set of chemicals that transform the feeling of fullness into a hunger that is never quite satisfied. Intriguingly, people who smoke cannabis regularly do not tend to gain weight – if anything they are less likely to be obese. This property makes cannabis appealing for those suffering from various illness that affects appetite.

Dr. Mark Ware, Associate Professor in Family Medicine and Anesthesia at McGill University, conducted the first ever long term study on the effects of medical cannabis; he studied 216 individuals with chronic pain and 215 controls (chronic pain but no current cannabis use) from seven clinics across Canada. They found the reduction in pain from using 2.5g herbal cannabis per day was statistically significant but lower than expected.

Concerning the therapeutic properties of THC and other cannabinoids against cancer, anecdotal evidence abounds but the science itself is far more debatable.Researchers first began studying the anti-cancer properties of cannabinoids back in the 1970s, and many hundreds of scientific papers looking at cannabinoids and cancer have been published since then, according to Cancer Research UK. The problem is virtually all of them have been done using cancer cells grown in the lab or animal models, and a lot of times such findings can’t be translated to humans. Moreover, some studies suggest that although high doses of THC can kill cancer cells, they also harm crucial blood vessel cells. Cancer cells can develop resistance to cannabinoids and start growing again.

According to Cancer.gov, “the only published trial of any cannabinoid in patients with cancer is a single, small study of intratumoral injection of delta-9-THC in patients with recurrent glioblastoma multiforme, which demonstrated no significant clinical benefit.” All eight patients involved in the clinical trial died within a year. But because the trial showed some response,  cannabinoids are worth pursuing in clinical trials. Hopefully, we might learn more.

Dronabinol and Nabilone/Cesamet, two synthetic pill forms of THC, are FDA-approved and currently being used to treat nausea and vomiting associated with chemo.

 

 

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