Delta-9-Tetrahydrocannabinol (THC)

In Israel in 1964 the most prominent compound in Cannabis sativa L., a non-toxic herb commonly referred to simply as 'Cannabis', delta-9-Tetrahydrocannabinol (THC), was discovered. THC starts out in the Cannabis plant as geranyl pyrophosphate and olivetolic acid. Through enzyme catalisation (an increase in the rate of chemical reaction, without which most biochemical reactions would not occur) they become Cannabigerolic acid (CBG-a), the essential precursor for all cannabinoids. CBG-a becomes THC-a, a cannabinoid which has very different effects to THC. But, with heat or over time, THC-a decarboxylates into THC. Cannabinoids are specialised molecules that mimic similar chemicals in the human body and fit into special receptors within the brain, nervous and immune systems and as reported in the scientific literature at this time there are around 111 known natural cannabinoids. 

Cannabinoids have been found to work synergistically with the human body and, more specifically, the Endogenous Cannabinoid System (ECS). The human body produces its own cannabinoids, called endocannabinoids (endogenous means produced internally). Phytocannabinoids (literally, 'plant' cannabinoids) from the Cannabis plant are a perfect fit for the specialised cannabinoid receptors found throughout the brain, nervous and immune systems. In addition, cannabinoids do more than work independently to deliver a particular therapeutic effect, they also work in tandem to regulate one another, something that has been labelled the Entourage Effect. These miracle molecules give the herb a wide variety of therapeutic benefits, from reducing inflammation to managing pain and many researchers and patients have begun to recognise the fact that single cannabinoid extracts may not be the best solution for the majority of patients.

The Endocannabinoid System (ECS) is a coordinated network that consists of the canonical Cannabinoid Receptors (CB1 and CB2), their endogenous ligands, Anandamide (the 'bliss' molecule) and 2-arachidonoyl glycerol (2-AG) and their synthesising and degrading enzymes. THC mimics the actions of Anandamide and 2-AG and has been shown to be an effective treatment for a variety of neurological, gastrointestinal and psychological ailments. It is an especially effective treatment for Crohn’s disease. This is primarily because of the way in which this cannabinoid decreases inflammation, the core cause of Crohn's. In fact, THC is such an effective treatment for Crohn’s, it has been shown to put the disease into remission. Strains high in THC are also effective in treating PTSD and even preventing heart attacks. Strains high in THC can sometimes deliver a strong dose of paranoia but this is easily ameliorated with everyday household pantry items like Black Pepper, and patients who suffer from acute anxiety often find strains lower in THC to be more therapeutic. Cannabichromene (CBC) another cannabinoid, has been found to enhance the potency of THC. Thus, a strain that is high in both THC and contains enough CBC to enhance its psychoactive properties will be especially potent, providing greater efficacy for some patients. Likewise, another cannabinoid, Cannabigerol (CBG), has the opposite effect on THC, serving to buffer its effects and decrease its psychoactive properties. Strains that are high in THC, but also with sufficient amounts of CBG, may be more tolerable for some.

The commercial value in most jurisdictions where use of Cannabis is still illegal is typically dictated by the amount of THC it contains. Cannabis strains with larger percentages of THC (12-21% is purportedly the average) are capable of delivering more potent therapeutic and medicinal efficacy. Some strains of Cannabis, such as Train Wreck and OG Kush, feature THC in quantities as high as 24-30%. Concentrates, such as hash and wax may feature as much as 85% THC. One method of isolating the THC contained in whole plant Cannabis is to vaporise it, allowing it to be consumed without the tars and toxins of smoking.

THC is a bronchial dilator, an effective treatment for asthma and related respiratory conditions, again this is due to its anti-inflammatory properties. It is also very helpful for those suffering from autoimmune deficiencies, such as wasting syndrome and HIV/AIDS, because of its ability to stimulate a patient’s appetite. THC allows sufferers to maintain body weight and enjoy proper nutrition so they are most capable of battling their disease. THC is a powerful treatment for nausea caused by chemotherapy and other toxic treatments. It allows patients to keep down food or critical pharmaceutical drugs that otherwise would be lost through vomiting. Like its cousin Cannabidiol (CBD), THC also provides neuroprotective qualities, making it well suited to treating diseases like Multiple Sclerosis (MS), Parkinson’s and Epilepsy. Like CBD, CBG and CBC, THC has also been proven to fight cancer and can be an effective analgesic (pain killer). 


THC has been proven completely safe to consume with decades of research revealing the impossibility of overdose. According to the United States (US) National Cancer Institute, “Because cannabinoid receptors, unlike opioid receptors, are not located in the brain-stem areas controlling respiration, lethal overdoses from Cannabis and cannabinoids do not occur”. Lethal doses are simply not possible due to the lack of cannabinoid receptors in the brain stem, responsible for respiration and heart function, unlike drugs such as cocaine and heroin, which can easily result in overdose. In 2008, researchers in universities in both Montreal and Vancouver, Canada, reviewed 23 clinical investigations of cannabinoid drugs (typically oral THC or liquid pharmaceutical Cannabis extracts) and eight observational studies conducted between 1966 and 2007. Investigators "did not find a higher incidence rate of serious adverse events associated with medical cannabinoid use" compared to non-using controls over these four decades.

Regulation of THC by other cannabinoids like CBG also affect potency and overall effect, providing another buffer. A 2009 study revealed that using only 10 times the “effective” dose of alcohol can be fatal, whereas 1,000 times the effective amount would be necessary to achieve a fatal dose of Cannabis, a quantity impossible to consume! More research has indicated additional reasons why humans don’t die from Cannabis poisoning. In 2014, the journal Science published results from a French study, Pregnenolone Can Protect the Brain from Cannabis Intoxication, which documented the discovery and presence of a natural hormone that reverses Cannabis intoxication - in rats, at least. According to the researchers: “When the [rat] brain is stimulated by high doses of THC, it produces pregnenolone - a 3,000% increase - that inhibits the effects of THC”.  

Therapeutic and medicinal values include (but are certainly not limited to):

♋ Analgesic (Pain Killer) – Understanding the mechanism of cannabinoid-induced analgesia has been increased through the study of cannabinoid receptors, endocannabinoids, and synthetic agonists and antagonists. The CB1 receptor is found in both the central nervous system (CNS) and in peripheral nerve terminals. One of the most common uses of Cannabis is for pain relief and THC is the cannabinoid responsible for its pain-relieving effects. A 2010 double-blind study titled "Smoked Cannabis for Chronic Neuropathic Pain: A Randomized Controlled Trial", published in the Canadian Medical Association Journal stated: "Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive Cannabis at four potencies (0%, 2.5%, 6% and 9.4% THC) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. Conclusion: A single inhalation of 25mg of 9.4% THC herbal Cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated". A 2012 study shows THC activates pathways in the central nervous system which work to block pain signals from being sent to the brain. Likewise, in a 2013 study, Cannabis is shown to be especially effective against neuropathic pain, or nerve-related pain. Another 2013 study titled, "Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain", published in the Journal of Pain stated; "Cannabis has analgesic efficacy with the low dose (1.29%) being, for all intents and purposes, as effective a pain reliever as the medium dose (3.53%). Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporised Cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain". A quick search via Google Scholar returns around 26,900 results for THC as an analgesic and over 3,000 of those results are from 2015.

♋ Anti-emetic (Nausea and Vomiting) – In 2001 a Post-doctoral Fellow in the Department of Psychiatry at the University of Chicago (Illinois, US) wrote an article, "Antiemetic Efficacy of Smoked Marijuana: Subjective and Behavioral Effects on Nausea Induced by Syrup of Ipecac" in the journal Pharmacology, Biochemistry and Behavior which stated; "The present study examined the antiemetic effect of smoked Cannabis cigarettes (8.4 and 16.9mg THC) compared to a highly potent antiemetic drug, ondansetron (8mg) in 13 healthy volunteers. Nausea and emesis were induced by syrup of ipecac. Cannabis significantly reduced queasiness and slightly reduced the incidence of vomiting compared to placebo. Ondansetron completely eliminated the emetic effects of ipecac. These findings support and extend previous results, indicating that smoked Cannabis reduces feelings of nausea and also reduces emesis in this model". THC has to be dosed relatively highly, so any resultant side effects may occur comparatively frequently and more recent investigations have shown THC in low doses improves the efficacy of other anti-emetic drugs if given together. There is evidence from clinical studies that cannabinoids are effective in nausea and vomiting due to radiotherapy and after surgery. Cannabinoids are popular in alternative and complementary medicine and are often used in other causes of nausea including AIDS, Hepatitis and nausea in pregnancy.

Synthetic THC has been available in pill form and used for treating nausea and vomiting in cancer patients since the 1980's. In the US, a growing number of cancer patients and oncologists view Cannabis as a viable alternative for managing chemotherapy’s effects, as well as some of the physical and emotional health consequences of cancer, such as bone pain, anxiety and depression. Marinol® was the first synthetic THC pharmaceutical to be approved by the US Food and Drug Administration (FDA) for this purpose. Since then, other THC pills have been developed and prescribed to patients undergoing chemotherapy. However, the danger with synthesising any plant extract is that you lose the intrinsic checks and balances provided by nature and undesirable side-effects ensue. For example, Marinol® causes more psychoactive effects than natural, organic THC! Nature is always best, even when the pharmaceutical industry tries to tell us otherwise!

♋ Appetite Stimulant - Along with its ability to reduce nausea, THC is known to work as a powerful appetite stimulant in both healthy and sick individuals (whole organic Cannabis promotes a healthy appetite). As Professor of Clinical Medicine (University of California, San Francisco), Dr Donald Abrams says Cannabis “is the only anti-nausea medicine that increases appetite”. Cannabis also helps Dr Abrams' patients sleep and elevates their mood which is no easy feat when someone is facing a life-threatening illness. “I could write six different prescriptions, all of which may interact with each other or the chemotherapy that the patient has been prescribed. Or I could just recommend trying one medicine”, Dr Abrams said.

♋ Asthma - THC’s ability to improve breathing in asthmatics is supported by research examining the anti-asthmatic effect dating from the 1970's. In Australia, up until the 1920's, 'Cigares de Joy' (Joy's Cigarettes), which were Cannabis cigarettes or 'joints' were sold. "Joy's Cigarettes afford immediate relief in cases of Asthma, Wheezing and Winter Cough, and a little perseverance will effect a permanent cure", read the 1920's advertising blurb! Following trials in the first half of the 1970's that showed smoking Cannabis could help calm asthma attacks, scientists tried to develop an inhaler that could deliver THC, and some say vaporisers might be the solution. The effects of a Cannabis cigarette (2% THC) or oral THC (15 mg), respectively, approximately correspond to those obtained with therapeutic doses of common bronchodilator drugs (for example, salbutamol).

♋ Crohn's Disease – A prospective trial in Israel showed complete remission in five of eleven patients suffering Crohn's Disease who were given Cannabis twice daily. Authors of the study said it had been reported for years that Cannabis lessened the painful symptoms of the inflammatory bowel disease, but findings had not been proven in a controlled trial. The 2013 study, published in Clinical Gastroenterology and Hepatology compared 21 patients who did not respond to conventional treatment. Half were given Cannabis cigarettes and the other half were given placebo (Cannabis cigarettes with the THC removed). Results showed improvement in the group treated with the THC-intact Cannabis. Those subjects also reported improved sleep and appetite. The 8-week treatment with THC-rich Cannabis caused a decrease in the Crohn's Disease activity index in 90% of patients without producing significant side effects. The mechanisms involved most likely include peripheral actions on cannabinoid receptors 1 and 2 (CB1 and CB2) and may also include central actions.

♋ Epilepsy – One of the mechanisms underlying the anticonvulsant properties of cannabinoids is through their activation of CB1. THC has shown CB1-dependent anticonvulsant activity in experimental models of seizure and epilepsy. Cannabis has some contradictory effects in Epilepsy which likely has to do with the complexity of the plant itself. Cannabis not only exhibits many cannabinoids, it exhibits other compounds including potentially neuroactive substances such as terpenes, hydrocarbons, ketones, aldehydes and other hydrophobic compounds capable of crossing the blood–brain barrier. The variability of the strain-specific ratios of the most common cannabinoid, THC, and the second most common cannabinoid, CBD, offers further complexity in utilising whole Cannabis as an anti-epileptic. In addition, the mode of administration likely affects bio-availability and neuroactivity. However, there is evidence that Oral Cannabis Extracts (OCEs) are well tolerated by children and adolescents with Epilepsy, according to a 2015 study, Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy, in the journal, Epilepsy & Behavior.

♋ Glaucoma – Glaucoma causes patients to develop a reduced field of vision that can lead to blindness. Glaucoma is incurable and the second leading cause of blindness in the world, according to the World Health Organization. There are actually several different types of Glaucoma, but only two are common. These two are characterised by an increase in intraocular pressure (IOP), or pressure inside the eye (shown in the diagram), which damages the optic nerve. The cause of the increase in eye pressure is similar, but different between the two most common types. A benefit of THC, recognised early on, was its potential to relieve eye pressure in patients with glaucoma. Studies in the 1970's showed that smoking Cannabis could reduce symptoms in Glaucoma sufferers and scientists tried (and failed) to develop a way to administer THC in eye drops. The idea proved too complicated due to THC not being soluble in water. In 2004 in an article titled "Glaucoma", by GW Pharmaceuticals Cannabinoid Research Institute stated; "The ability of Cannabis and THC to lower intra-ocular pressure in Glaucoma was serendipitously discovered in the late 1970's by a variety of patients and researchers. Several patients in the US Compassionate Use Investigational New Drug Program maintained their vision while employing large amounts of daily Cannabis in situations where standard drug therapy failed ... An emerging concept is that Glaucoma represents a progressive vascular retinopathy that requires a neuroprotectant to preserve vision. Some of the resulting optic nerve damage accrues due to NMDA hyperexcitability, an effect that THC and CBD may counter as neuroprotective antioxidants. Thus, Glaucoma is an area where Cannabis and cannabinoids may offer particular advantages over available single ingredient ocular anti-hypertensive agents".

♋ HIV/AIDS (Acquired Immunodeficiency Syndrome) – The American Academy of HIV Medicine (AAHIVM) stated in 2007, "When appropriately prescribed and monitored, Cannabis can provide immeasurable benefits for the health and well-being of our patients". Also in 2007, Dr Donald Abrams, Professor of Clinical Medicine (University of California, San Francisco) wrote an article; Cannabis in Painful HIV-Associated Sensory Neuropathy: A Randomized Placebo-Controlled Trial, in the journal Neurology: "Objective: To determine the effect of smoked Cannabis on the neuropathic pain of HIV-associated sensory neuropathy, and an experimental pain model ... Patients were randomly assigned to smoke either cannabis (3.56% THC) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days ... Conclusion: Smoked Cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain". A group of researchers from Louisiana State University (US) published a study in 2014 in the journal AIDS Research and Human Retroviruses which suggests Cannabis can help stop the progression of HIV/AIDS and its associated symptoms of chronic pain, nausea, fatigue and more. The specific compound that halts the spread of HIV compounds into other healthy cells is none other than THC.

♋ Multiple Sclerosis (MS) – A 2001 study, "Prospects for New Cannabis-Based Prescription Medicines", published by GW Pharmaceuticals in the Journal of Cannabis Therapeutics stated; "In practice it has been found that extracts of Cannabis (processed whole plant compounds) provide greater relief of pain than the equivalent amount of cannabinoid given as a single chemical entity (such as Marinol) .... Some patients with Multiple Sclerosis who smoke Cannabis report relief of spasm and pain after the second or third puff of a Cannabis cigarette. This implies very rapid transit to, and absorption into the central nervous system. The time involved is seconds rather than minutes". In a 2012 study, "Multiple Sclerosis and Extract of Cannabis: Results of the MUSEC Trial", published in the Journal of Neurology, Neurosurgery & Psychiatry, patients with stable MS across the United Kingdom (UK) were randomised to oral Cannabis Extract (CE) or placebo. This was a Double Blind, Placebo controlled, Phase III study with a screening period, a 2 week dose titration phase from 5-25mg of THC daily and a 10 week maintenance phase. The rate of relief from muscle stiffness after 12 weeks was almost twice as high with CE than with placebo. In conclusion, the study met its primary objective to demonstrate the superiority of CE over placebo in the treatment of muscle stiffness in MS. At the Hebrew University of Jerusalem in August 2015, researchers took isolated immune cells, which target and harm the brain and spinal cord, from paralysed mice and treated them with either THC or CBD. In both cases, the immune cells produced fewer inflammatory molecules, strongly associated with MS and very harmful to nerve cells and their insulating covers. Researchers concluded the presence of THC or CBD restrains the immune cells from triggering the production of inflammatory molecules and limits the molecules' ability to reach and damage the brain and spinal cord. Researchers say further studies are needed to prove the effectiveness of cannabinoids in treating MS in humans but in many countries, THC and CBD are already prescribed for the treatment of MS symptoms, including pain and muscle stiffness.

♋ Post Traumatic Stress Disorder (PTSD) - The euphoric 'high' from THC is associated with temporary impairment of memory. While this may be seen as a drawback for some Cannabis users, impaired memory is often therapeutic for those who struggle to forget painful memories, such as patients who suffer from PTSD. In 2014, research out of Israel confirmed oral doses of THC can help relieve a variety of PTSD-related symptoms including flashbacks, agitation and nightmares. In a 3-week pilot study involving 10 patients with severe PTSD, oral doses of THC led to significant improvement across a number of measures, including sleep and hyperarousal symptoms. The findings were published in the journal Clinical Drug Investigation. The researchers wrote, “The results show good tolerance and safety, reduction of PTSD hyperarousal symptoms, improved sleep quality and reduced frequency of nightmares”. Recent evidence suggests cannabinoids may enhance the ability to overcome traumatic memories. What’s more, cannabinoids are known to affect sleep in various ways, including a decrease in REM sleep — the sleep phase during which nightmares occur. Anecdotal reports also suggest Cannabis may be of benefit. Also in 2014, psychometric data on PTSD symptoms collected during 80 psychiatric evaluations of patients applying to the New Mexico (US) Medical Cannabis Program between 2009-20011 was statistically analysed. PTSD symptoms were reduced by more than 75% in patients using Cannabis ...". The 2015 study, Use and effects of cannabinoids in military veterans with Post Traumatic Stress Disorder, concluded; "evidence indicates that substantial numbers of military veterans with PTSD use Cannabis or derivative products to control PTSD symptoms, with some patients reporting benefits in terms of reduced anxiety and insomnia and improved coping ability".

♋ Sleep Aid – The sleep-inducing effects of Cannabis are well known and research shows that THC is largely responsible. In fact, trials conducted in the 1970's found oral doses of THC helped both healthy individuals and insomniacs fall asleep faster. More recent studies suggest THC may also improve night-time breathing and reduce sleep interruptions in those who suffer from a common disorder known as Sleep Apnoea.

♋ Tourette Syndrome (TS) – In 2003, the Director of the Tourette Syndrome Clinic at the Medical School of Hannover stated, THC was "effective and safe in the treatment of tics" from Tourette syndrome, following a Double-Blind Study, "Delta 9-Tetrahydrocannabinol (THC) Is Effective in the Treatment of Tics in Tourette Syndrome: A 6-Week Randomized Trial", which was published in the Journal of Clinical Psychiatry. "In this randomised, double-blind, placebo-controlled study, 24 patients with TS (according to DSM-III-R criteria) were treated over a 6-week period with up to 10 mg/day of THC and found a significant difference or a trend toward a significant difference between THC and placebo groups ... at 10 treatment days (between days 16 and 41) there was a significant difference between both groups and no serious adverse effects occurred ... results provide more evidence that THC is effective and safe in the treatment of tics. It, therefore, can be hypothesised that the central cannabinoid receptor system might play a role in TS pathology". Regardless of any personal opinion one may hold on the use of Cannabis, a firm grasp of the facts is necessary to overcome an abundance of misinformation, particularly from mainstream media and those with a vested interest in keeping Cannabis illegal (researchers and government/s reliant on 'donations' from pharmaceutical companies, for example). More research is certainly still necessary to even begin to fully comprehend the seemingly endless applications and benefits of THC and the sometimes extremely subtle ways in which it interacts with a variety of other phyto and endocannabinoids (and that's just for starters). Despite the ability of high-THC strains to cause confusion and anxiety in some patients (easily ameliorated as noted above), THC will continue to be the focus not only of users of Cannabis, but of medical researchers, and as more is learned about its function/s and how it interacts with other cannabinoids, new strains will be bred and natural extracts developed that better target particular illnesses and diseases for the benefit of all humankind.

This is Part 4a of a series covering the major branches of cannabinoids. Parts 1 to 3 covered the other major branches; Part 1 - CBG-a, The Precursor, and CBG. Part 2 covered Cannabidiols (CBD's) including Cannabidiolic acid (CBD-a). Part 3 covered Cannabichromenes (CBC's), including Cannabichromenic acid (CBC-a). Parts 4b and 4c will cover Tetrahydrocannabinolic acid (THC-a) along with Delta-8-Tetrahydrocannabinol, Cannabinolic-acid (CBN-a) and Cannabinol (CBN).

Resources;

What is THC?, 7 Proven Medical Benefits of THC, How do THC, CBD, CBN Relate to Marijuana Potency?, Cannabinoids - Learn, No Official Lethal Dose For Cannabis, Safety Profile of Medical Cannabis - NORML, Cannabis and Crohn's, The Case For Medical Marijuana In Epilepsy, Is Marijuana an Effective Treatment for Glaucoma?, Using Cannabis to Treat Glaucoma, Marijuana Could Help Treat MS, Cannabis Treats PTSD Symptoms - Pilot Study, 60 Peer Reviewed Studies on Medical Marijuana and Granny Storm Crow's List 2015