Cannabis in Therapeutic Applications

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Table of Contents

Introduction
Mechanism of Action
Medical Treatment
Conclusion
References

Introduction

Cannabis, also known as marijuana, is one of the most commonly misused drugs in western cultures for recreational purposes. The drug was reported to have approximately 192 million users as of 2018 worldwide (Gabri et al., 2022). In Europe alone, almost 90 million people ranging between 15-64 years reported to have taken marijuana at least once in their lifetime, and about 1 in every 10 young adults used the drug monthly in 2019 (Gabri et al., 2022). Additionally, the United States recorded 3.43 million users in 2020 (Conway, 2022). The inappropriate use and sake of cannabis may contain significant public health as well as social consequences. When compared with non-user individuals, monthly consumption of the drug is assumed to lead to an increased risk of injuries, psychosis, and poor obstetric outcomes. Furthermore, cannabis is addictive and causes cognitive impairment and short-term memory (Yu et al., 2020). Moreover, cannabis misuse is directly linked with reduced motivation and poor academic performance. As much as the use of cannabis is associated with adverse effects, its health effects, such as pain reduction, remain beneficial.

Mechanism of Action

The mechanism of action of marijuana in the human body remains unclear. Marijuana is the only plant that comprises Cannabinoids which contain similar properties to the endocannabinoids found in the human body. The drug contains over 400 compounds of the terpenoid and flavonoid types and its chemical elements known as cannabinoids, with more than 60 being pharmacologically active (Rabipour et al., 2022). All the cannabinoids are capable of activating endogenous receptors of the CB1 and CB2 type in the endocannabinoid system. CB1 and CB2 then trigger specific signaling systems that initiate various actions by directly obstructing the release of several neurotransmitters, including dopamine, acetylcholine, and glutamate (Rabipour et al., 2022). The endocannabinoid system is a dense network of organs all over the body that express the receptors and take homeostatic functions (Anand et al., 2021). CB1 receptors are primarily located in the hippocampus, spinal cord, basal ganglia, peripheral nerves, association cortex, and cerebellum, whereas the CB2 receptors are situated in the immune system’s cells. The roles of the endocannabinoid system include memory, appetite, pain, immunity, movement, cardiopulmonary function, salivation or lacrimation, and metabolism.

The majority of the effects of cannabinoids, like psychotropics, result from CB1 activation, with CB2 taking significant roles in inflammatory and immune functions. Internally, endocannabinoids act as modulators of neuro-regulation, which are responsible for reverse neurotransmission (Anand et al., 2021). A post-synaptic neuron at this point excretes endocannabinoids that combine mainly with CB1 receptors on the presynaptic nerve cell. The joining with the CB1 receptors then leads to inhibited activation of the presynaptic calcium channel and the release of subsequent presynaptic neurotransmitters. Suppose the presynaptic neurotransmitters are primarily inhibitory, like Gamma-aminobutyric acid (GABA), the net outcome will be excitatory. Moreover, binding to distinct parts of the central nervous system (CNS) mediates diverse cannabinoids’ psychotropic traits, specifically THC. The affected areas and their effects include impairment of short-term memory in the hippocampus, altered movement and reaction time in basal ganglia, and euphoria in the nucleus accumbens (Anand et al., 2021). Additionally, there is impaired sensation and judgment in the neocortex, increased appetite in the hypothalamus, ataxia in the cerebellum, analgesia in the spinal cord, and paranoia and panic in the amygdala.

Cannabidiol (CBD) which contains antipsychotic and anxiolytic effects, and delta-9-tetrahydrocannabinol (THC), which is the primary psychoactive marijuana component, are the most studied cannabinoids. The main source of THC is the resin of stems or leaves, and it is highly fat soluble. Additionally, THC is quickly absorbed in the intestinal and respiratory systems with a bioavailability of 6% when consumed orally and between 15-20% when smoked (Rabipour et al., 2022). The therapeutic effects of cannabis are reliant on THC concentration as well as the cannabidiol to THC ratio following the ability of cannabidiol to moderate THC psychoactive effects. The 1:1 ratio has been reported to produce the best clinical advantages with less adverse effects (Rabipour et al., 2022). Moreover, the channel of administration is significant as it establishes the absorption process, pharmacology as well as the metabolism of various cannabinoids. The cannabinoids’ therapeutic properties include neuroprotective, antioxidant, antiviral, bone stimulant, antibiotic, anti-inflammatory, and vasorelaxant.

Medical Treatment

Pain Management

Marijuana can be used as an effective remedy for pain reduction. Cannabinoids extracted from cannabis have been investigated for their analgesic benefits in pain management, such as cancer-associated pain, particularly neuropathic pain (Daris et al., 2019). In support of this, Donk et al. (2018) found that more patients showed pain reduction by 30% with high doses of CBD and THC. CB1 receptors in the central nervous system exist in concentrated amounts in brain areas that mediate nociceptive processing with the same distribution as opioid receptors (Anand et al., 2021). Additionally, cannabinoids may act on mast cell receptors which promote the release of analgesic opioids to curb inflammation and hinder the emission of inflammatory substances, thereby reducing pain effects.

Moreover, cannabinoids inhibit the acute pain response fibers as well as the wind-up phenomenon, which are largely associated with hyperalgesia development hence helping with the treatment of neuropathic pain. Cannabinoids can be combined with opioids to produce analgesia using the G-protein coupled mechanism that inhibits the release of pain-generating neurotransmitters in the spinal cord as well as the brain (Anand et al., 2021). Furthermore, the analgesic effect of cannabinoids THC is moderated through kappa and delta opioid receptors depicting a close connection between opioid and cannabinoid signaling channels in the variation of pain perception.

Anxiety Disorders and Post-Traumatic Stress Disorder (PTSD)

Anxiety disorders and PTSD are regarded as the most common mental diseases globally, accompanied by high financial and psychosocial burdens, especially in veterans. They are primarily treated with psychotherapy, benzodiazepines, and antidepressants containing selective norepinephrine and serotonin reuptake inhibitor as well as a serotonin reuptake inhibitor. However, even with these treatments, approximately 40% of patients continue to experience anxiety and PTSD symptoms which have then motivated medical experts to seek effective therapeutics. CBD has shown to be an alternative therapeutic treatment for anxiety and PTSD. Elms et al. (2019) found that an oral administration of CBD to regular psychiatric care led to reduced PTSD symptoms in 91% of adults in their study. In addition, their results indicated that CBD provided relief for patients that have frequent encounters with nightmares as a PTSD symptom. Moreover, Shannon et al. (2019) claimed that anxiety scores dropped in 79.2% of their participants, while 66.7% reported increased sleep scores within the first month of the research. Therefore, it is evident that CBD can be an effective treatment for PTSD and anxiety.

Increasing the consumption of cannabinoids such as CBD helps the level of joy transmitter, that is, anandamide, increase, which helps eliminate undesirable encounters. Moreover, the resultant change in body chemicals aid in soothing an individual’s muscles and nerves which allows relaxation, thus reducing the effects of anxiety. Anandamide acts as a neurotransmitter since they transmit chemical messages between neurons in the nervous system. CBD affects various parts of the brain, which influence memory, sensory perception, thinking, as well as coordination (Elms et al., 2019). THC contains this same feature which enables it to bind with receptors in the brain, stimulating several physical and mental features. Furthermore, recreational smoking of marijuana has been associated with short-term memory loss among individuals. Despite this, examination of the endocannabinoid system indicates that it helps accelerate the process of enabling people to forget painful experiences, including traumatic events.

Seizure

Cannabidiol can be used to prevent some forms of seizures in some individuals, such as ones suffering from epilepsy. Some epilepsy patients suffer from drug-resistant epilepsy. A drug-resistant epilepsy patient is one whose seizures are uncontrollable despite using the required dosage of not less than two antiepileptic medications. Drug-resistant epilepsy reduces the quality of life of individuals, increases cognitive problems, and leads to severe psychosocial consequences (Gray & Whalley, 2020). Endocannabinoids take part in reducing excitatory neurotransmitter release in the central nervous system, which aids in inhibiting seizure development. They work on cannabinoid receptors, with CB1 being expressed in peripheral and neural nerve cells and CB2 in brain cells as well as the immune cells. CBD interacts with the purinergic system to increase extracellular adenosine, which reduces seizure threshold generation. In support of this, Zafar et al. (2021) found an 86% decrease in seizure frequency in all of their 10 participants and reported reduced use of antiepileptic drugs following medical cannabis treatment. Moreover, seizures initiate the rapid production and release of adenosine and 2-arachidonoylglycerol (2-AG), which can be provided by marijuana, hence reducing seizure frequency.

Loss of CB1 and CB2 receptors influences the regulation of neural activity, which can lead to severe and spontaneous forms of seizures. For this reason, formulating and creating drugs containing cannabinoid receptors can be used as a therapeutic way to help reduce the development of seizure disorders (Gray & Whalley, 2020). Since CBD has more antiepileptic features than THC, drugs containing more CBD are most effective in seizure reduction. Moreover, CBD contains fewer adverse effects due to its weak activity at CB1 and CB2 receptors working as an effective remedy for seizure with less adverse effects (Zafar et al., 2021). Furthermore, CBD operates under other mediums, such as transient receptor potential (TRP) channels leading to a reduction in the glutamate presynaptic release, thereby lowering seizure incidences.

Nausea

Nausea is a common symptom of various illnesses but is considered challenging to treat using conventional treatments. It is caused by various problems such as chemotherapy, gastrointestinal disorders, emotional distress, and food poisoning. Cannabis has been widely used to curb nausea, and its effectiveness has been recorded mostly in cancer chemotherapy. Marijuana contains high concentrations of THC compound, which affects the dorsal vagus nerve and is responsible for moderating vomiting and nausea (Mersiades et al., 2018). The drug has the ability to induce responses of the CB1 receptor to other stimuli like the insular cortex in the CNS. In addition, CBD promotes CB1 expression in the hypothalamus, which is responsible for appetite and helps relax the digestive tract, which helps reduce nausea incidences. CBD enhances the synthesis of particular hormones, such as ghrelin which induces appetite or the drive to eat.

Moreover, CBD promotes the production of serotonin and dopamine, otherwise known as mood hormones which can be beneficial for individuals lacking appetite in stressful situations. Dopamine initiates a hunger feeling which then promotes appetite (Mersiades et al., 2018). On the other hand, serotonin aids in moderating digestive-related processes such as appetite and bowel movements. Additionally, CBD can directly bind with CB2 receptors found in the peripheral tissues, like in the gastrointestinal system, which then helps in the synthesis of stomach acid and saliva. Thus, CBD can be helpful in promoting hunger and effective digestion.

Conclusion

In conclusion, cannabis can be used for medical purposes despite having severe effects. The mechanism of action of cannabis continues to be unclear, even with diverse research. Marijuana contains cannabinoids with similar properties to endocannabinoids found in the human body. Cannabinoids activate CB1 and CB2 receptors which trigger specific signaling systems that initiate various actions by directly obstructing the release of several neurotransmitters. Most cannabinoid effects, such as psychotropics, result from CB1 activation, with CB2 taking significant roles in inflammatory and immune functions. Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are the most studied components of cannabinoids.

Cannabis can be used in pain management, particularly in cancer patients. Cannabinoids may act on mast cell receptors which promote the release of analgesic opioids, thus helping in pain reduction. Moreover, cannabinoids inhibit the acute pain response fibers as well as the wind-up phenomenon, which largely contributes to neuropathic pain reduction. Additionally, marijuana is highly effective in the treatment of anxiety disorders and post-traumatic stress disorder. Increasing the consumption of cannabinoids helps the level of joy transmitters which helps eliminate traumatic experiences. Cannabinoids are able to influence an individual’s thinking, coordination, memory, and sensory perception allowing THC to attach itself to neurons and influence outcomes. Cannabidiol can be used to prevent some forms of seizures. Endocannabinoids take part in reducing the release of excitatory neurotransmitters in the (CNS), inhibiting seizure development. Furthermore, cannabis contains high concentrations of THC compound, which affects the dorsal vagus nerve and is responsible for moderating vomiting and nausea. CBD promotes the production of ghrelin, serotonin, and dopamine beneficial for individuals lacking appetite.

References

Anand, U., Pacchetti, B., Anand, P., & Sodergren, M. (2021). Cannabis-based medicines and pain: A review of potential synergistic and entourage effects.Pain Management, 11(4), 395–403. Web.

Conway, J. (2022). Number of adult-use cannabis users in the United States from 2020 to 2025. Statista. Web.

Daris, B., Verboten, M., Knez, Ž., & Ferk, P. (2019). Cannabinoids in cancer treatment: Therapeutic potential and legislation. Bosnian Journal of Basic Medical Sciences, 19(1), 14–23. Web.

Donk, T., Niesters, M., Kowal, M. A., Olofsen, E., Dahan, A., & Velzen, M. (2018). An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain, 160(4), 860–869. Web.

Elms, L., Shannon, S., Hughes, S., & Lewis, N. (2019). Cannabidiol in the treatment of post-traumatic stress disorder: A case series. The Journal of Alternative and Complementary Medicine, 25(4), 392–397. Web.

Gabri, A., Galanti, M., Orsini, N., & Magnusson, C. (2022). Changes in cannabis policy and prevalence of recreational cannabis use among adolescents and young adults in Europe-an interrupted time-series analysis. PLOS ONE, 17(1), 1–10. Web.

Gray, R., & Whalley, B. (2020). The proposed mechanisms of action of CBD in epilepsy.Epileptic Disordorders, 22(1), 10–15. Web.

Mersiades, A., Tognela, A., Haber, P., Stockler, M., Lintzeris, N., Simes, J., McGregor, I., Olver, I., Allsop, D., Gedye, C., Kirby, A., Morton, R., Fox, P., Clarke, S., Briscoe, K., Aghmesheh, M., Wong, N., Walsh, A., Hahn, C., & Grimison, P. (2018). Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: A study protocol for a pilot and definitive randomised double-blind placebo-controlled trial (CannabisCINV). BMJ Open, 8(9), 1–8. Web.

Rabipour , S., Mahmood, E., & Afsharkhas, M. (2022). Medicinal use of marijuana and its impacts on respiratory system. Journal of Chemistry Letters, 3(2), 86–94. Web.

Shannon, S., Lewis, N., Lee, H., & Hughes, S. (2019). Cannabidiol in anxiety and sleep: A large case series. The Permanente Journal, 23(1), 1–5. Web.

Yu, B., Chen, X., Chen, X., & Yan, H. (2020). Marijuana legalization and historical trends in marijuana use among US residents aged 12–25: Results from the 1979–2016 national survey on drug use and health.BMC Public Health, 20(1), 1–10. Web.

Zafar, R., Schlag, A., Phillips, L., & Nutt, D. (2021). Medical cannabis for severe treatment resistant epilepsy in children: A case-series of 10 patients. BMJ Paediatrics Open, 5(1), 10–15. Web.

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