The role of medical cannabis on the treatment of pain
Introduction
Pain is an uncomfortable sensation that can range from mild to severe and is a common symptom of many medical conditions. Pain can significantly reduce the quality of life and interfere with daily activities. Traditional pain management options such as opioids have been associated with various side effects and the risk of addiction. This has led to increased interest in alternative treatment options, including medical cannabis. In recent years, medical cannabis has emerged as a promising treatment for pain. In this article, we will discuss why medical cannabis is useful in treating pain.
Overview of Medical Cannabis
Medical cannabis is a plant-based medication that contains over 100 active compounds known as cannabinoids. The most well-known cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is responsible for the psychoactive effects of cannabis, while CBD has no psychoactive effects. Medical cannabis is available in various forms, including oils, tinctures, capsules, and vaporisers.
How Medical Cannabis Treats Pain
The human body contains an endocannabinoid system (ECS) that plays a crucial role in regulating various physiological processes, including pain. The ECS consists of three main components: endocannabinoids, receptors, and enzymes. Endocannabinoids are molecules produced naturally by the body that bind to cannabinoid receptors. The two primary cannabinoid receptors are CB1 and CB2. CB1 receptors are mainly found in the brain and central nervous system, while CB2 receptors are primarily found in the immune system and peripheral tissues.
The cannabinoids found in medical cannabis can interact with the ECS and modulate the pain response. THC, the psychoactive compound in cannabis, can activate CB1 receptors in the brain and spinal cord, leading to pain relief. THC can also increase the release of dopamine, a neurotransmitter that can provide a sense of euphoria and reduce anxiety and depression.
CBD, on the other hand, can interact with various receptors in the body, including serotonin and vanilloid receptors, to provide pain relief. CBD has also been found to have anti-inflammatory properties, which can reduce inflammation and pain.
Medical Cannabis for Chronic Pain
Chronic pain is a persistent pain that lasts for more than three months. Chronic pain can significantly reduce the quality of life and interfere with daily activities. Medical cannabis has shown promise in managing chronic pain. A 2015 systematic review of randomised controlled trials found that medical cannabis can provide a significant reduction in chronic pain in adults. The review also found that medical cannabis was well-tolerated and had a low risk of serious adverse effects.
A 2018 systematic review and meta-analysis of randomised controlled trials found that medical cannabis can significantly reduce chronic neuropathic pain. The review also found that medical cannabis can provide a reduction in the use of opioids and improve the quality of life in patients with chronic pain.
Medical Cannabis for Cancer Pain
Cancer pain is a common symptom in patients with advanced cancer. Cancer pain can be challenging to manage and can significantly reduce the quality of life in patients. Medical cannabis has shown promise in managing cancer pain. A 2017 systematic review and meta-analysis of randomized controlled trials found that medical cannabis can provide a significant reduction in cancer-related pain. The review also found that medical cannabis was well-tolerated and had a low risk of serious adverse effects.
Medical Cannabis for Neuropathic Pain
Neuropathic pain is a type of pain caused by damage or dysfunction of the nervous system. Neuropathic pain can be challenging to manage and can significantly reduce the quality of life in patients. Medical cannabis has shown promise in managing neuropathic pain. A 2018 systematic review and meta-analysis of randomized controlled trials found that medical cannabis can significantly reduce neuropathic pain
Research on the role of medical cannabis on treating pain
1.Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action
Abstract
Cannabis has a long history of medical use. Although there are many cannabinoids present in cannabis, Δ9tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the two components found in the highest concentrations. CBD itself does not produce typical behavioral cannabimimetic effects and was thought not to be responsible for psychotropic effects of cannabis. Numerous anecdotal findings testify to the therapeutic effects of CBD, which in some cases were further supported by research findings. However, data regarding CBD’s mechanism of action and therapeutic potential are abundant and omnifarious. Therefore, we review the basic research regarding molecular mechanism of CBD’s action with particular focus on its analgesic potential. Moreover, this article describes the detailed analgesic and anti-inflammatory effects of CBD in various models, including neuropathic pain, inflammatory pain, osteoarthritis and others. The dose and route of the administration-dependent effect of CBD, on the reduction in pain, hyperalgesia or allodynia, as well as the production of pro and anti-inflammatory cytokines, were described depending on the disease model. The clinical applications of CBD-containing drugs are also mentioned. The data presented herein unravel what is known about CBD’s pharmacodynamics and analgesic effects to provide the reader with current state-of-art knowledge regarding CBD’s action and future perspectives for research.
2. Evaluation of the preclinical analgesic efficacy of naturally derived, orally administered oil forms of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their 1:1 combination
Abstract
Chronic neuropathic pain (NP) is a growing clinical problem for which effective treatments, aside from non-steroidal anti-inflammatory drugs and opioids, are lacking. Cannabinoids are emerging as potentially promising agents to manage neuroimmune effects associated with nociception. In particular, Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination are being considered as therapeutic alternatives for treatment of NP. This study aimed to examine whether sex affects long-term outcomes on persistent mechanical hypersensitivity 7 weeks after ceasing cannabinoid administration. Clinically relevant low doses of THC, CBD, and a 1:1 combination of THC:CBD extracts, in medium chain triglyceride (MCT) oil, were orally gavaged for 14 consecutive days to age-matched groups of male and female sexually mature Sprague Dawley rats. Treatments commenced one day after surgically inducing a pro-nociceptive state using a peripheral sciatic nerve cuff. The analgesic efficacy of each phytocannabinoid was assessed relative to MCT oil using hind paw mechanical behavioural testing once a week for 9 weeks. In vivo intracellular electrophysiology was recorded at endpoint to characterize soma threshold changes in primary afferent sensory neurons within dorsal root ganglia (DRG) innervated by the affected sciatic nerve. The thymus, spleen, and DRG were collected post-sacrifice and analyzed for long-term effects on markers associated with T lymphocytes at the RNA level using qPCR. Administration of cannabinoids, particularly the 1:1 combination of THC, elicited a sustained mechanical anti-hypersensitive effect in males with persistent peripheral NP, which corresponded to beneficial changes in myelinated Aβ mechanoreceptive fibers. Specific immune cell markers associated with T cell differentiation and pro-inflammatory cytokines, previously implicated in repair processes, were differentially up-regulated by cannabinoids in males treated with cannabinoids, but not in females, warranting further investigation into sexual dimorphisms that may underlie treatment outcomes.
3. The effects of cannabidiol and analgesic expectancies on experimental pain reactivity in healthy adults: A balanced placebo design trial.
Abstract
Despite its frequent use for pain relief, no experimental pain research has tested the analgesic effects of cannabidiol (CBD) in humans. The goal of this study was to experimentally test the effects of CBD and expectancies for receiving CBD on human pain reactivity. Using a crossover, 2 × 2 factorial balanced placebo design, drug administration (given inactive substance or given active CBD) and verbal instruction sets (told inactive substance or told active CBD) were experimentally manipulated. Fifteen healthy adults each completed four separate experimental sessions. Participants were randomly assigned to different counterbalanced manipulation conditions at each session: control (told inactive—given inactive); expectancy (told active CBD—given inactive); drug (told inactive—given active CBD); and expectancy + drug (told active CBD—given active CBD). Primary outcomes were pain threshold, tolerance, intensity, unpleasantness, conditioned pain modulation (CPM), and offset analgesia (OA). There was a significant main effect of instructions on OA, such that the OA response was significantly larger when participants were told that they received CBD, regardless of drug content. Pain unpleasantness was significantly reduced in the drug, expectancy, and expectancy + drug conditions, relative to the control condition. The drug and expectancy conditions separately improved CPM, whereas the expectancy + drug and control conditions produced the lowest CPM change scores. We did not detect significant effects for pain threshold, tolerance, or intensity. Our results indicated that separate pain outcomes can be differentially affected by CBD and/or expectancies for receiving CBD. Future investigations of the psychological and pharmacological mechanisms underlying CBD analgesia are warranted. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
4. A Balanced Approach for Cannabidiol Use in Chronic Pain
Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa L., has gained traction as a potential treatment for intractable chronic pain in many conditions. Clinical evidence suggests that CBD provides therapeutic benefit in certain forms of epilepsy and imparts analgesia in certain conditions, and improves quality of life. CBD continues to be Schedule I or V on the list of controlled substances of the Drug Enforcement Agency of the United States. However, preparations labeled CBD are available publicly in stores and on the streets. However, use of CBD does not always resolve pain. CBD purchased freely entails the risk of adulteration by potentially hazardous chemicals. As well, CBD use by pregnant women is rising and poses a major health-hazard for future generations. In this mini-review, we present balanced and unbiased pre-clinical and clinical findings for the beneficial effects of CBD treatment on chronic pain and its deleterious effects on prenatal development.
Introduction
Cannabis and its components are being widely used for chronic pain, especially given the multifaceted and persistent nature of chronic pain in many conditions (Kalant, 2001). Cannabidiol (CBD), one of the major phytocannabinoids, has gained significant attraction because it is devoid of the psychoactive effects associated with tetrahydrocannabinol (THC), another major constituent of cannabis (Leweke et al., 2012). With the recent rescheduling (Schedule V) of CBD as Epidiolex for the treatment of Dravet and Lennox-Gastaut syndromes there has been a major shift in the view of these ancient molecules for their medicinal potential (Laux et al., 2019). Preclinical and clinical studies have indicated a potential benefit of CBD use in chronic pain associated with multiple conditions (Wade et al., 2003). However, increasing access to cannabis derived products especially CBD partly because of their approval for recreational and medicinal use in the United States poses risks with inadvertant side-effects from overuse, contamination with adulterants in preparation or harsh chemicals in the plant cultivation, and its teratogenicity in the offspring of users (Bonn-Miller et al., 2017; Young-Wolff et al., 2017; Rubin, 2019). In this mini-review we will evaluate literature discussing CBD use in treating intractable pain and the potential hazards of its overuse and/or misuse.
5. Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?
Abstract
The interest in cannabis-based products for the treatment of refractory epilepsy has skyrocketed in recent years. Marijuana and other cannabis products with high content in Δ(9) - tetrahydrocannabinol (THC), utilized primarily for recreational purposes, are generally unsuitable for this indication, primarily because THC is associated with many undesired effects. Compared with THC, cannabidiol (CBD) shows a better defined anticonvulsant profile in animal models and is largely devoid of adverse psychoactive effects and abuse liability. Over the years, this has led to an increasing use of CBD-enriched extracts in seizure disorders, particularly in children. Although improvement in seizure control and other benefits on sleep and behavior have been often reported, interpretation of the data is made difficult by the uncontrolled nature of these observations. Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a turning point in the last 12 months, with the completion of three high-quality placebo-controlled adjunctive-therapy trials of a purified CBD product in patients with Dravet syndrome and Lennox-Gastaut syndrome. In these studies, CBD was found to be superior to placebo in reducing the frequency of convulsive (tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet syndrome, and the frequency of drop seizures in patients with Lennox-Gastaut syndrome. For the first time, there is now class 1 evidence that adjunctive use of CBD improves seizure control in patients with specific epilepsy syndromes. Based on currently available information, however, it is unclear whether the improved seizure control described in these trials was related to a direct action of CBD, or was mediated by drug interactions with concomitant medications, particularly a marked increased in plasma levels of N-desmethylclobazam, the active metabolite of clobazam. Clarification of the relative contribution of CBD to improved seizure outcome requires re-assessment of trial data for the subgroup of patients not comedicated with clobazam, or the conduction of further studies controlling for the confounding effect of this interaction.