Did you know that there is a system in our bodies comprised of receptors that interact exclusively with cannabinoids like CBD and THC?. Recent science has found that the endocannabinoid system does not just respond to . While THC has a strong binding affinity for both CB1 and CB2 receptors. After several decades of research, scientists studying the effects of marijuana made several important discoveries. Not only did they identify the active ingredient.
Endocannabinoid and CBD, System the THC
Review Figure 1 and the steps below to take a closer look at the components of the EC system, how it works, and the effects of THC. Typically, the chemicals called neurotransmitters are released from a neuron a presynaptic cell , travel across a small gap the synapse , and then attach to specific receptors located on a nearby neuron postsynaptic cell.
This spurs the receiving neuron into action, triggering a set of events that allows the message to be passed along. Then they are released from that cell and travel backward to the presynaptic neuron, where they attach to cannabinoid receptors.
So why is this important? Since cannabinoids act on presynaptic cells, they can control what happens next when these cells are activated. When a person smokes marijuana, THC overwhelms the EC system, quickly attaching to cannabinoid receptors throughout the brain and body. CBD does not bind directly to either of these receptors but instead impacts them indirectly. These indirect actions include activating TRPV1 Receptors that work to control important functions like pain perception, body temperature, and inflammation.
CBD can also increase the amount of anandamide in the body. By stimulating the endocannabinoid system, CBD promotes homeostasis, reduces pain sensation and decreases inflammation.
The endocannabinoid system's purpose is to respond to endogenous cannabinoids produced within the human body. During their research, scientists have learned that the system will also recognize and respond to cannabinoids from external sources, including the phytocannabinoid cannabidiol CBD. According to the National Institute of Health , manipulating the endocannabinoid system by introducing external cannabinoids like CBD could be useful in treating a variety of medical ailments, including: Keep in mind that this CBD benefits chart is not a full list, and we are only beginning to discover how cannabinoids can help and heal.
To date, experts agree there are two types of cannabinoid receptors; cannabinoid receptor type 1 CB1 and cannabinoid receptor type 2 CB2. These neurons act as a sort of lock, with cannabinoids acting as the key. Although they have similar sounding names, these two receptors perform very different functions in the human body.
CB1 receptors first discovered in exist in high numbers in the brain especially the hypothalamus, hippocampus, and amygdala , central nervous system CNS , intestines, connective tissues, gonads, and various other glands. While these are desirable effects for most people, CB1 receptor activation does not come without risks. Please note that these are most often side effects associated with chronic consumption of a potent CB1 receptor agonist such as THC, and not with a non-psychoactive substance such as CBD.
CB2 receptors first discovered in occur most commonly in the spleen, tonsils, thymus, and immune cells such as mast cells, monocytes, macrophages, B and T cells, and microglia; only a small number exist in the brain. Changes in CB2 receptor function is synonymous with virtually every type of human disease; be it cardiovascular, gastrointestinal, neurodegenerative, psychiatric, and autoimmune.
However, compounds blunting severe pain allow patients to perform daily activities more easily, so the potential benefits should be weighed against possible adverse effects. Our current understanding of the physiology and pharmacology of the endogenous cannabinoid system has motivated cannabis-based therapeutic drug design, in which attempts are being made to synthesise compounds with the desired therapeutic actions but without psychoactive adverse effects.
Medications prepared with cannabinoid receptor agonists or with drugs that enhance endocannabinoid function by either increasing release or diminishing reuptake of endocannabinoids may afford the novel therapeutic approaches demanded by disorders in which pain is a prominent symptom. Clinical trials seem to indicate that either extracts of the Cannabis sativa plant containing known amounts of the active compounds mainly THC and CBD or diverse synthetic derivatives of THC are promising treatments for painful conditions that do not respond to available treatments, such as neuropathic, inflammatory and oncologic pain.
Specifically, cannabis extracts have shown effectiveness to relief some symptoms of the patients with multiple sclerosis, mainly for pain and spasticity. Pharmacologic manipulation directed to elevate endocannabinoids levels like, for example, with anandamide reuptake inhibitors, or by inhibiting the enzyme fatty acid amide hydrolase FAAH , which is responsible for intracellular anandamide degradation, may well become a valuable therapeutic tool.
CB2 receptor selective agonists with no central effects are other promising pain treatment under investigation. Adequately sized and designed, doubleblind placebo-controlled clinical trials are needed to evaluate the potential applications of cannabis-based medications as novel and effective therapeutic drugs for controlling different types of pain.
We wish to thank Mr. National Center for Biotechnology Information , U. Journal List Curr Neuropharmacol v. Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Abstract Cannabis extracts and synthetic cannabinoids are still widely considered illegal substances.
Analgesia, cannabidiol, cannabinoid receptor, cannabis, endocannabinoid, inflammatory pain, neuropathic pain, tetrahydrocannabinol. Open in a separate window.
Endocannabinoids The endocannabinoids, or endogenous cannabinoids, are a family of bioactive lipids that activate cannabinoid receptors to exercise their effects, modulating neural transmission. Animal Models of Pain Different validated animal models are used to explore the analgesic effects of cannabinoid compounds.
Sites of Pain Modulation When investigating cannabinoid actions in the control of pain, special consideration should be given to the level at which such actions take place to determine whether the mechanisms are central or peripheral. Wind-up Phenomenon Wind-up is an exaggerated neuronal response that occurs upon repeated noxious stimulation, residing at the synapse between the primary afferent and the spinothalamic neuron. Vanilloid Receptor Type One VR 1 Not all antinociceptive effects of cannabinoid compounds are mediated by cannabinoid receptors.
Interactions Between Cannabinoids and Prostaglandin Inhibitors and COX-2 An interaction between cannabinoids and inhibitors of prostaglandin biosynthesis like NSAIDs has been reported, and it appears to be due to the similarity in chemical structure of endogenous cannabinoid ligands and prostaglandins arachidonic acid derivatives , and to the convergence of prostaglandin and endocannabinoids transduction signals [ 36 ]. Thermal stimuli Antinociceptive effects which remained after memory and psycholinguistic effects were returning to normal levels i.
The reason could be a biphasic effect, with initial stimulation followed by sedation. Electrical and pressure stimuli No analgesic effect of THC, but methodological problems: They did not include a positive control; like an established analgesic as opiate or narcotic.
Antinociceptive effects during the first two weeks of smoking, then returning to presmoking pain level maintained during the postsmoking period. Heavy smoking caused increase in pain reports.
Thermal stimuli Cannabis dose-dependent antinociceptive effects. Naltrexone randomised, double-blind did not influence cannabis effects, suggesting no role of endogenous opiates in cannabis-induced antinociception under these conditions. Randomised, double-blinded, placebo-controlled, crossover. Pain tests order randomised: THC did not significantly reduce pain. In the cold and heat tests it even produced hyperalgesia, which was completely neutralized by THC-morphine.
Psychotropic and somatic side effects sleepiness, euphoria, anxiety, confusion, nausea, dizziness, etc. THC analgesic effects less than that after diazepam and placebo, while pain detection thresholds were altered unpredictably with high THC doses.
Three subjects at low-dose THC had a better analgesic effect than placebo but not diazepam. Six subjects preferred placebo to low-dose THC as an analgesic. Significant analgesic effects of each dose of levonantradol a synthetic cannabinoid as compared to placebo. No analgesic effect of THC in this paradigm. Randomisation took place when postoperative patient-controlled analgesia was discontinued on the second postoperative day.
Tolerance to cannabis was not reported. Medical cannabis use associated with male gender, tobacco use, and recreational cannabis use. Symptoms most effectively relieved: THC and codeine both had an analgesic effect as compared with placebo.
Only THC showed a significant beneficial effect on spasticity. THC did no alter consciousness. A significant number of patients abandon the drug because dysphoria and drowsiness. Patients who had used cannabis for chronic pain prior to trying nabilone a synthetic analogue of THC preferred the former Karst et al.
Adverse effects, mainly transient: No major adverse effects were observed. MS 18 , spinal cord injury 4 , brachial plexus damage 1 , and limb amputation 1. Three patients had transient hypotension and intoxication with rapid initial dosing of THC. Cannabis medicinal extracts improved neurogenic symptoms unresponsive to standard treatments.
Unwanted effects are predictable and generally well tolerated. Parallel group, double-blind, randomised, placebo-controlled study, undertaken in three centres. MS patients experiencing significant problems: The primary symptom score reduced more with CBME, but not significantly different than placebo.
Spasticity was significantly reduced by CBME compared with placebo. No significant adverse effects on cognition or mood, and intoxication was generally mild. Extracts containing THC proved most effective in symptom control. Wide range of dosing requirements was observed. Side effects were generally acceptable and little different to those seen when other psychoactive agents used for chronic pain.
Randomised, double-blind, placebo-controlled, three period crossover study. Significant improvement on pain severity and on sleep disturbances. Generally well tolerated, majority of adverse events being mild to moderate in severity and resolving spontaneously. Studies of longer duration in neuropathic pain are required to confirm a clinically relevant, improvement in the treatment of this condition.
Acute Pain Opioids are powerful analgesics widely utilised in clinical pain management, but they yield a poor analgesic response in conditions of certain pathologic pain, such as neuropathy. Postoperative Pain One potential indication of cannabinoids would be as analgesic for postoperative pain.
Chronic Pain Multiple Sclerosis Multiple sclerosis MS is a life-long chronic disease in which nerve cells are attacked by the immune system, originating painful muscle spasms and many other problems, including neuropathic pain.
Neuropathic Pain Neuropathic pain, which is frequently chronic, arises when neurons in the brain or peripheral nervous system become hypersensitised and generate abnormal or prolonged impulses. Cancer Pain Pain is one of the most frequent symptoms in patients with cancer and the World Health Organisation recommends that they receive adequate pain relief. References Treatment Results and Remarks Noyes et al. Each patients all treatments Double blind placebo-controlled trial preliminary.
Analgesic effect of THC at high doses 15 and 20 mg , significantly superior than placebo. At these doses, substantial sedation and mental clouding. No nausea or emesis. Increased appetite in some patients. Mild analgesic effect of THC. At 20 mg THC similar to mg codeine induced side effects that would prohibit its therapeutic use, including somnolence, dizziness, ataxia, and blurred vision; and even some alarming adverse reactions.
At 10 mg THC similar to 60 mg codeine: Double-blind, 5-way crossover designed study. Significant analgesic relief with mg of codeine, but no differences between placebo and benzopyranopyridine analogue of THC.
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Cannabinoid science. Medical marijuana research led to the discovery of The Endocannabinoid System, an important system in the human body. The endocannabinoid system (ECS) is deeply involved in the complex .. As THC, CBD, and CBN did not have any estrogenic actions on their own, either the . Nonetheless, the discovery of the endogenous cannabinoid system in the early s Pain relief by both THC and CBD significantly superior to placebo.