An Introduction to Medical Uses of THC

The uses of tetrahydrocannabinol (THC) as a medicinal compound has a long history, from its first recorded medical use in 400 AD to its wide use as a patent medicine during the 19th and early 20th centuries (1). However, despite scientists ongoing research efforts, there are still marked difference in what we know about the medical uses of cannabis and cannabinoids like THC in different diseases.

For instance, cannabis has been shown to help support patients suffering from nausea and vomiting associated with chemotherapy, bulimia and cachexia in HIV/AIDS. Similarly, when it comes to chronic neuropathic pain, as well as spasticity in multiple sclerosis and spinal cord injury, there is strong evidence to suggest the medical benefits of THC. In contrast, for other diseases such as psychiatric disorders, asthma, glaucoma and epilepsy, there is much less data available.

This, however, does not mean that a lack of scientific evidence for a specific disease does not necessarily mean that there is no actual therapeutic potential of medical cannabis and THC for that given disease.

Incidental and clinical observations, as well as positive anecdotal experiences, also have validity when it comes to revealing therapeutical effect and positive medical uses. A prime example of this was the accidental discovery in the 1970s that THC decreases intraocular pressure (2). Similarly, the results of a retrospective chart review reported at the 11th congress of the International Psychogeriatric Association by Patel and colleagues showed that not only does THC show potential appetite-stimulating in Alzheimer patients with anorexia but that disturbing behaviour among the patients also decreased (3).

Surveys are another way in which interesting THC applications that have not been scientifically investigated can be gauged. For this reason, data from self-reporting by individuals that use cannabis therapeutically have been conducted. Either as anonymous surveys using standardized questionnaires or non-standardized oral interviews by state or scientific institutions (e.g., House of Lords Select Committee on Science and Technology in the UK, Institute of Medicine in the USA) (4, 5, 6).

From all of the above sources, from peer-reviewed scientific sources, patient charts or self-reported data from medical cannabis users, there is a picture emerging that common problems in modern medicine may benefit from treatment with cannabis or cannabinoids such as THC.

In this report, we will look at some of the diseases for which we have evidence in support of the potential for the efficacy of THC in treating these, dividing it into two sections: Section 1 covering disease for which we have strong scientific data, Section 2 looking at more anecdotal evidence.

Scientific Evidence for the Medical Uses of THC

Medical Uses of THC in Anorexia-Cachexia

Anorexia and cachexia are medical conditions that cause extreme weight loss and muscle wasting in patients. Although anorexia is most often associated with self-starvation, along with cachexia, it is also a symptom of many chronic conditions, such as cancer, chronic renal failure, Alzheimer's, HIV, and multiple sclerosis.

The appetite enhancing effect of THC is well known among recreational users of cannabis. However, more recently, researchers have investigated the medical use of THC in clinical populations suffering from anorexia and/or cachexia.

In a review of THC in the treatment of patients with anorexia/cachexia syndrome, the authors concluded that THC had considerable potential to improve the appetite, body weight, body fat level, caloric intake, mood, quality of life not only in cancer patients but also other kinds of diseases (7). In another review study that investigating the effectiveness of THC for the treatment of cachexia in HIV-positive patients, six studies of over 298 patients, the data showed that THC can have a positive effect on improving appetite and weight gain in HIV-positive patients (8).

Similarly, in a placebo-controlled crossover design, researchers investigated the effects of dronabinol (a synthetic THC) in 15 patients with a diagnosis of probable Alzheimer's disease who were refusing food. Results from this study indicated that THC shows promise as a therapeutic agent not only for the treatment of anorexia, but also for improving disturbed behavior in patients with Alzheimer's disease (9).

Medical Uses of THC in Alzheimer’s Disease & Dementia

Alzheimer’s disease, is a chronic neurodegenerative disease that usually starts slowly and gradually worsens over time and is the underlying cause of 60–70% of cases of dementia. The most common symptoms include difficulty in remembering recent events, problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, not managing self-care, and behavioural issues.

THC for supporting patients with Alzheimers disease and dementia is a popular research topic, with studies investigating its potential use in symptoms such as nighttime agitation (10), neuropsychiatric symptoms and behavioural disturbances (11), cognitive impairments (12) and even gait and balance (13).

The most promising use of THC in Alzheimers disease and dementia is that of its potential neuroprotective effects due to the wain which it interacts with the endocannabinoid system that may offer protection against the deleterious consequences of neuroinflammation, excitotoxicity and neurotoxicity. There is also some evidence that cannabinoids may regulate the release of endocannabinoids involved with neurogenesis (14).

Medical Use of THC for Inflammation

Inflammation is the primary cause of a number of painful disorders and conditions including autoimmune diseases, coeliac disease, hepatitis, inflammatory bowel disease, and rheumatoid arthritis. THC may act not only as an analgesic but also potential anti-inflammatory effects.

Recent animal studies show that THC administration triggers marked apoptosis (normal cell death) in T cells and dendritic cells, resulting in immunosuppression. Also, several studies have also shown that THC can downregulate cytokine and chemokine production responsible for signalling molecules that mediate and regulate immunity and inflammation. Some models also show that THC potentially up-regulates T-regulatory cells as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in the regulation of the immune system and inflammation and the manipulation of endocannabinoids by means of exogenous cannabinoids such as THC may be a potent treatment option against inflammatory disorders (15).

Medical Use of THC for Glaucoma & Occular Pressure

Glaucoma is a group of eye conditions that damage the optic nerve, the health of which is vital for good vision. This damage is caused by an abnormally high interocular pressure, or pressure in the eye that initially results in the loss of peripheral vision, and eventually resulting in blindness.

During a systematic investigation of the effects of cannabis in healthy users in 1971, researchers observed that it reduced intraocular pressure. In the years following from then, a number of studies in both healthy individuals and glaucoma patients, shows the potential of THC for decreasing intraocular pressure by an average 25-30%, occasionally up to 50%. Scientist observed that this is potentially due to the changes in ocular pressure paralleling with the changes in blood pressure in each glaucoma patient (16).

In one randomized, double-masked, placebo-controlled, 4 way crossover study, researchers assessed the effect, safety and tolerability of THC on intraocular pressure (IOP). Results indicated that of the six patients with ocular hypertension or early primary open-angle glaucoma who received THC, a single 5 mg sublingual dose of Delta-9-THC reduced the IOP temporarily and was well tolerated by most patients (17).

Medical Use of THC in Multiple Sclerosis & Spasticity

Multiple Sclerosis is a disabling disease in which the immune system attacks the protective sheath (myelin) that covers nerve fibers. This causes communication problems between the brain and the rest of your body, primarily resulting in numbness, weakness or electric-shock sensations as well as spasticity and tremors.

Several clinical trials of THC and its synthetic derivatives indicated a beneficial effect on spasticity caused by multiple sclerosis (18) and/or spinal cord injury (19). Among other positively influenced symptoms were pain (20), paraesthesia, tremor (21) and ataxia (22).

Medical Use of THC for Nausea & Vomiting

THC’s antiemetic effects are most well-known for the treatment of side effects associated with chemotherapy, with studies going as far back as the mid 1070s (23). Since then, the Federal Drug Adminstration (FDA) approved both dronabinol and nabilone in 1985 for treatment of chemotherapy-induced nausea and vomiting (CINV).

Researchers theorise that when THC binds to the CB1 receptors in specific parts of the brain, it acts as an antiemetic, reducing nausea and vomiting (24). Since then, several clinical trials involving 1,366 patients (sixteen trials assessing nabilone, and thirteen trials studying dronabinol) have been conducted indicating that synthetic cannabinoids are better than traditional antiemetic medications for CINV. In fact, these trials also showed that cannabinoids like THC alleviated CINV more effectively than either metoclopramide or placebos in all trials (26).

Medical Use of THC for Neuropathic Pain

Neuropathic pain is pain caused by damage or disease to the somatosensory nervous system and is usually associated with abnormal sensations called dysesthesia, or pain from normally non-painful stimuli (allodynia). It may be chronic in nature, but can also come-and-go for some patients.

Large clinical studies have proven the analgesic properties of THC. The Center for Medicinal Cannabis Research (CMCR) at the University of California completed five placebo-controlled phase II clinical trials with smoked or inhaled cannabis and another study from Canada investigated the efficacy and safety of THC-rich medical cannabis. Patients included people with HIV, neuropathy and other neuropathic conditions suffering from neuropathic pain. Overall, the efficacy of THC/medical cannabis was comparable to that of traditional medications. In addition, the efficacy THC was comparable to gabapentin, however somewhat less than that of the tricyclics, but better than SSRIs and anticonvulsants used for pain relief (25 - 31).

Anecdotal Evidence for the Medical Uses of THC

There are some positive anecdotal reports of therapeutic response to THC for a variety of other medical conditions, although these are either much less thoroughly researched, and/or from surveys or qualitative studies relying on self-reported data.

For instance, some medical cannabis patients report symptom relief from Tourette's syndrome, dystonia (involuntary muscle contractions) and tardive dyskinesia (involuntary stiff, jerky movements of your face and body resulting from antipsychotic medications). THC for use in Tourette's syndrome is currently being investigated in clinical studies, with many patients achieving none or only modest improvement. However, some show a considerable response or even complete symptom control (32 - 34).

Although the administration of THC benefits ataxia and reduces tremors in some multiple sclerosis patients, no objective symptom improvements have been found in Parkinsonism (35 - 36). However, some patients report that THC-rich cannabis products help improve symptoms of Parkinson’s disease in the initial stages of treatment without any major adverse side effects (37). Similarly, some motor symptom improvements have been seen with Huntington’s disease (38).

There are also a number of positive patient reports on medical conditions including pruritus (itching of the skin) (39), hiccups (40), tinnitus (ringing in the ears) (41), Isaac’s syndrome (a neuromuscular disorder characterized by progressive muscle stiffness, continuously contracting or twitching muscles and diminished reflexes) (42), restless leg syndrome (43 - 44), to name a few.

Various researchers, medical and psychiatric professionals have expressed different viewpoints regarding the use of THC and/or medical cannabis for psychiatric syndromes. Most are concerned about the problems caused by cannabis use, especially in relation to psychosis. However, with increasing data become available from animal studies, preliminary clinical trials and case reports showing some preliminary benefits of THC for some psychiatric symptoms, others do promote THC’s therapeutic possibilities. Some psychiatric symptoms that could benefit from certain therapeutic properties of THC and cannabis include certain sleep disorders (45), anxiety disorders (46 - 47), depression (48), bipolar disorders (49), and post-traumatic stress disorder (50).

Final Thoughts

The above is not intended to be an all-inclusive list of symptoms, diseases and disorders that can potentially benefit from the medical use of THC. Instead, our aim is to give a brief survey of the types of conditions for which medical cannabis and THC can provide relief, with links to controlled human clinical trials as supportive evidence.

It is also important to bear in mind that the only cannabinoid-based drugs approved by the FDA are Epidiolex, dronabinol (Marinol, Syndros) and nabilone (Cesamet). Epidiolex is a cannabidiol (CBD) based drug approved in 2018 for treating seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. Dronabinol and nabilone are two synthetic forms of THC approved to treat nausea and vomiting from chemotherapy.

As with all therapeutic agents, medial claims regarding its efficacy must be critically evaluated and treated with caution.

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