The cannabis-derived chemical is non-psychoactive, and – while federally illegal – has been hailed as a cure for disease. Cannabidiol (CBD) is an active ingredient in cannabis derived from the Now I am not surprised they take this natural healing substance and. In just a few years, cannabidiol (CBD) has become immensely in a large survey among medicinal cannabis users published in .
cannabinoid CBD Healing
A pilot study published in Addictive Behaviors found that smokers who used inhalers containing CBD smoked fewer cigarettes than usual and had no further cravings for nicotine. A similar review, published in Neurotherapeutics found that CBD may be a promising treatment for people with opioid addiction disorders. The researchers noted that CBD reduced some symptoms associated with substance use disorders. These included anxiety , mood-related symptoms, pain, and insomnia.
More research is necessary, but these findings suggest that CBD may help to prevent or reduce withdrawal symptoms. After researching the safety and effectiveness of CBD oil for treating epilepsy, the FDA approved the use of CBD Epidiolex as a therapy for two rare conditions characterized by epileptic seizures in The types of seizures that characterize LGS or DS are difficult to control with other types of medication.
The FDA specified that doctors could not prescribe Epidiolex for children younger than 2 years. A physician or pharmacist will determine the right dosage based on body weight. Authors of a review noted that CBD has anti-seizure properties and a low risk of side effects for people with epilepsy. Findings suggested that CBD may also treat many complications linked to epilepsy, such as neurodegeneration, neuronal injury, and psychiatric diseases. Another study, published in Current Pharmaceutical Design, found that CBD may produce effects similar to those of certain antipsychotic drugs, and that the compound may provide a safe and effective treatment for people with schizophrenia.
However, further research is necessary. Some researchers have found that CBD may prove to combat cancer. Authors of a review published in the British Journal of Clinical Pharmacology found evidence that CBD significantly helped to prevent the spread of cancer.
The researchers also noted that the compound tends to suppress the growth of cancer cells and promote their destruction. They pointed out that CBD has low levels of toxicity. They called for further research into its potential as an accompaniment to standard cancer treatments.
Doctors often advise people with chronic anxiety to avoid cannabis, as THC can trigger or amplify feelings of anxiousness and paranoia. However, authors of a review from Neurotherapeutics found that CBD may help to reduce anxiety in people with certain related disorders. According to the review, CBD may reduce anxiety-related behaviors in people with conditions such as:. The authors noted that current treatments for these disorders can lead to additional symptoms and side effects, which can cause some people to stop taking them.
No further definitive evidence currently links CBD to adverse effects, and the authors called for further studies of the compound as a treatment for anxiety.
Type 1 diabetes results from inflammation that occurs when the immune system attacks cells in the pancreas. Research published in by Clinical Hemorheology and Microcirculation found that CBD may ease this inflammation in the pancreas. This may be the first step in finding a CBD-based treatment for type 1 diabetes. A paper presented in the same year in Lisbon, Portugal, suggested that CBD may reduce inflammation and protect against or delay the development of type 1 diabetes. Acne treatment is another promising use for CBD.
The condition is caused, in part, by inflammation and overworked sebaceous glands in the body. A study published by the Journal of Clinical Investigation found that CBD helps to lower the production of sebum that leads to acne, partly because of its anti-inflammatory effect on the body. Sebum is an oily substance, and overproduction can cause acne.
Initial research published in the Journal of Alzheimer's Disease found that CBD was able to prevent the development of social recognition deficit in participants. This means that CBD could help people in the early stages of Alzheimer's to keep the ability to recognize the faces of people that they know.
This is the first evidence that CBD may slow the progression of Alzheimer's disease. Cannabis is legal for either medicinal or recreational use in some American states. Other states have approved the use of CBD oil as a hemp product but not the general use of medical marijuana. Some state and federal laws differ, and current marijuana and CBD legislation in the U. There is an ever-changing number of states that do not necessarily consider marijuana to be legal but have laws directly related to CBD oil.
The following information is accurate as of May 8, , but the laws change frequently. However, state legislators generally approve the use of CBD oil at various concentrations to treat a range of epileptic conditions. A full list of states that have CBD-specific laws is available here. Different states also require different levels of prescription to possess and use CBD oil. In Missouri, for example, a person can use CBD of a particular composition if they can show that three other treatment options have failed to treat their epilepsy.
Anyone considering CBD oil should speak with a local healthcare provider. They can provide information about safe CBD sources and local laws surrounding usage. This is one of more than 80 active chemicals in marijuana. The new product was approved to treat seizures associated with two rare, severe forms of epilepsy in patients two years of age and older. Many small-scale studies have looked into the safety of CBD in adults.
They concluded that adults tend to tolerate a wide range of doses well. Researchers have found no significant side effects on the central nervous system , the vital signs, or mood, even among people who used high dosages.
The most common side effect was tiredness. Also, some people reported diarrhea and changes in appetite or weight. Concerning the product that the FDA approved to treat two types of epilepsy, researchers noticed following adverse effects in clinical trials:.
The patient information leaflet notes that there is a risk of worsening depression or suicidal thoughts. It is important to monitor anyone who is using this drug for signs of mood change. Research suggests that a person taking the product is unlikely to form a dependency. There is often a lack of evidence regarding the safety of new or alternative treatment options. Usually, researchers have not performed the full array of tests. Anyone who is considering using CBD should talk to a qualified healthcare practitioner beforehand.
When drugs do not have FDA approval, it can be difficult to know whether a product contains a safe or effective level of CBD. Unapproved products may not have the properties or contents stated on the packaging. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver.
This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components. Cannabis, commonly known as marijuana, is a product of the Cannabis sativa plant and the active compounds from this plant are collectively referred to as cannabinoids. For several centuries, marijuana has been used as an alternative medicine in many cultures and, recently, its beneficial effects have been shown in: Cannabinoid pharmacology has made important advances in recent years after the discovery of the cannabinoid receptors CB1 and CB2.
Cannabinoid receptors and their endogenous ligands have provided an excellent platform for the investigation of the therapeutic effects of cannabinoids. However, CB1 expression is predominant in the CNS, especially on presynaptic nerves, and CB2 is primarily expressed on immune cells [ 5 , 6 ]. Arachidonic acid metabolites have been shown to exhibit properties similar to compounds found in Cannabis sativa.
These metabolites are hence referred to as endocannabinoids. These ubiquitous endogenous cannabinoids act as natural ligands for the cannabinoid receptors expressed in mammalian tissue, thus constituting an important lipid-signaling system termed the endocannabinoid system.
The endocannabinoid system is an important biological regulatory system that has been shown to be highly conserved from lower invertebrates to higher mammals [ 7 ]. Other than the lipid transmitters that serve as ligands for the cannabinoid receptors, the endocannabinoid family also comprises the enzymes for biosynthesis and degradation of the ligands. The endocannabinoids include N -arachidonoylethanolamine, anandamide AEA , 2-arachidonoyl glycerol 2-AG , N -arachydonoyldopamine, noladin ether and virodhamine.
AEA was discovered by Devane et al. It was found to exist in much higher concentration in serum and brain than AEA. Endocannabinoids are derivatives of arachidonic acid conjugated with either ethanolamine or glycerol.
They are synthesized on demand from phospholipid precursors residing in the cell membrane in response to a rise in intracellular calcium levels. Inside cells, endocannabinoids are catalytically hydrolyzed by the aminohydrolase fatty acid amide hydrolase FAAH , which degrades AEA into arachidonic acid and ethanolamine [ 11 ].
Fatty acid-binding proteins FABPs have been reported to play an important role as intracellular carriers in the transport of AEA from the plasma membrane to FAAH for their subsequent inactivation [ 12 ]. Studies to date indicate that the main pharmacological function of the endocannabinoid system is in neuromodulation: However, in the periphery, this system is an important modulator of the ANS, immune system and microcirculation [ 13 ].
Some well-known natural and synthetic cannabinoids and endocannabinoids are depicted in Table 1. Cannabinoids are potent anti-inflammatory agents and they exert their effects through induction of apoptosis, inhibition of cell proliferation, suppression of cytokine production and induction of T-regulatory cells Tregs.
In this review, we provide an in-depth description of all four different mechanisms and we further discuss the immunosuppressive properties of cannabinoids in the context of inflammatory and autoimmune disease states, triggered by cellular rather than humoral components of the immune system.
One major mechanism of immunosupression by cannabinoids is the induction of cell death or apoptosis in immune cell populations. Under normal conditions, apoptosis is required in order to maintain homeostasis and it involves morphological changes i. The extrinsic pathway of apoptosis is initiated with the ligation of death receptors i. The intrinsic pathway of apoptosis is initiated via mitochondria and caspase 9; cytochrome c and caspase 3 are the major players in the induction of cell death [ 14 , 15 ].
This study also showed that the process was mediated via activation of Bcl-2 and caspases [ 16 ]. It was difficult to demonstrate the apoptotic effects of THC on lymphocytes, in vivo , and our laboratory speculated that this might be due to rapid clearance of dead cells by phagocytic cells. The cells were incubated for 12—24 h ex vivo and, since the phagocytosis was excluded in the cultures, we detected significant levels of THC-induced apoptosis in T cells, B cells and macrophages [ 17 ].
We have also demonstrated that THC induced higher levels of apoptosis in naive lymphocytes, when compared with mitogen-activated lymphocytes, because activated cells downregulated the levels of CB2 on their cell surface [ 17 ]. Several studies also reported THC-induced apoptosis in antigen-presenting cells. Furthermore, THC increased Bcl-2 and caspase 1 activity in naive and lipopolysaccharide LPS -activated macrophages isolated from the peritoneal cavity of mice [ 16 ]. In addition, the use of synthetic CB2 agonist JWH treatment in vitro led to cell death via both the death-receptor pathway and the intrinsic pathway.
When JWH was administered in vivo , the antigen-specific response to Staphylococcal enterotoxin A was inhibited significantly [ 22 ]. It is important to note that, unlike in immune cells, cannabinoids can protect from apoptosis in nontransformed cells of the CNS, which can play a protective role in autoimmune conditions such as multiple sclerosis. In a different study by Jackson et al. In addition, caspase 3 activation was higher in knockout cultures, indicating a protective role of CB1 in neuronal cells [ 24 ].
Cytokines are the signaling proteins synthesized and secreted by immune cells upon stimulation. They are the modulating factors that balance initiation and resolution of inflammation. One of the possible mechanisms of immune control by cannabinoids during inflammation is the dys-regulation of cytokine production by immune cells and disruption of the well-regulated immune response [ 25 ].
Furthermore, cannabinoids may affect immune responses and host resistance by perturbing the balance between the cytokines produced by T-helper subsets, Th1 and Th2. However, the results were variable, depending on the cell line and the concentration used [ 26 ].
Both pro-inflammatory and anti-inflammatory effects of THC were demonstrated in this study, proposing that different cell populations have varied thresholds of response to cannabinoids. Interestingly, while the anti-inflammatory cytokine IL decreased following THC treatment, there was an increase in the proinflammatory cytokine IL In other studies, cannabinoid CP55, at nanomolar concentrations was shown to have a stimulatory effect on several cytokines in the human promyelocytic cell line HL [ 27 ].
In a different study, mice were challenged with Corynebacterium parvum, in vivo , following the administration of the synthetic cannabinoids WIN55, and HU The animals were then challenged with LPS. This effect was shown to be CB1 receptor dependent. During chronic inflammation, IL-6 suppression can decrease tissue injury [ 30 ]. AjA has been reported to prevent joint-tissue injury in animal models of adjuvant arthritis [ 31 ]. Recent studies showed that addition of AjA to human monocyte-derived macrophages in vitro reduced the secretion of IL-6 from activated cells, suggesting that AjA may have a value for treatment of joint inflammation in patients with systemic lupus erythematosus SLE , rheumatoid arthritis RA and osteoarthritis [ 32 ].
Recent in vitro studies have also shown the potent anti-inflammatory effect of synthetic cannabinoids CP55, and WIN55, Endocannabinoids have also been reported to affect the cytokine biology of various cell systems. Antiproliferative effects of endocannabinoids on cancer cell lines are well established and are discussed in the later section of the review.
However, AEA has also been reported to increase cytokine-induced proliferation. Mouse bone marrow cells, when cultured in the presence of IL-3 and AEA, were observed to produce more hematopoietic colonies than with IL-3 alone [ 35 ]. Furthermore, in undifferentiated and macrophage-like differentiated HL cells, 2-AG induced CB2-dependent acceleration in the production of IL-8 [ 37 ].
On a contrary note, cytokines have also been shown to affect the endocannabinoid system. Table 2 provides a summary of the effect of cannabinoids on cytokines and chemokines in various cell models [ 26 , 28 , 29 , 32 — 34 , 37 , 40 , 41 ]. CXC-chemokine ligand 8; ND: The action of these cells leads to the demyelination of nerve fibers and axons in the CNS of humans and results in many signs and symptoms, such as muscle spasms, tremor, ataxia, weakness or paralysis, constipation and loss of bladder control [ 42 ].
There is both anecdotal and clinical evidence to show the effectiveness of cannabinoids in the treatment of MS. In , a survey of MS patients 57 men and 55 women from the USA and UK was conducted; all of the patients were self-medicating with a form of cannabis.
Use of cannabinoids also improved objective test results such as hand-writing tests and bladder control tests [ 43 , 44 ]. In general, cannabinoids are useful in treating MS because they have neuroprotective as well as immunosuppressive properties [ 44 , 45 ]. In this section, we will focus on the latter and discuss the action of endogenous, natural and synthetic cannabinoids on immune cells within the CNS during MS. The destruction of the blood—brain barrier in MS is initiated by myelin-specific self-reactive T cells.
Infiltration of these cells into the spinal cord and CNS, and their subsequent activation, leads to the elimination of the myelin sheath around the nerves and axons [ 46 , 47 ]. More recently, Th17 cells have been shown to be involved in the pathogenesis of MS [ 48 , 49 ].
One mechanism of immunosuppression by cannabinoids is the induction of apoptosis and Sanchez et al. A CB1-mediated suppressive pathway has also been shown in myelin-specific T cells [ 24 ].
Microglial cells are the macrophages of the CNS and, during MS, they mediate tissue injury in two main ways: In the initial stages of inflammation, after activation, microglial cells present antigens to myelin-specific T cells, which results in the activation and proliferation of Th1 lineage cells.
The investigators confirmed this finding by studying the morphology of the cells reactive vs resting as well as by immunohistochemistry. In the later stages of disease, microglial cells secrete IL, IL and IL, nitric oxide and glutamate and contribute to myelin sheath destruction. IL drives the proliferation of Th1 cells while IL is important in the maintenance of Th17 cells.
A recent study by Correa et al. Cannabinoids also exert their immunosuppressive effects on astrocytes. During disease progression, astrocytes are activated to secrete cytokines, chemokines and nitric oxide, thereby contributing to the overall inflammatory response.
Because astrocytes express both CB1 and CB2 receptors, several studies investigated the inhibitory role of cannabinoids on this cell population in the context of MS.
The precise role of IL-6 in the CNS is still unclear; however, it has been reported that IL-6 secretion potentiates neuronal growth factor production. In , Sheng et al. The three main cell types that are involved in demyelination of the nerve fibers and axons in the CNS include activated T-cells, microglia and astrocytes. In activated T-cells, treatment with WIN 55,, AEA and JWH has been shown to inhibit cytokine production, infiltration of cells into the spinal cord and in vitro recall response to myelin oligodendrocyte glycoprotein by T-cells.
Cannabinoids also inhibit the antigen presenting abilities of microglia by downregulating MHCII expression, costimulatory molecule CD40 expression, as well as cytokine secretion. Astrocytes, the major cell population in the brain, are also affected, as cannabinoid binding to the receptors leads to inhibition of inflammatory molecules, such as nitric oxide, cytokines and chemokines.
In addition, anandamide binding leads to secretion of neural growth factor secretion and protection of the neurons in the CNS. During inflammation, several different cellular pathways are activated in the intestinal tract, leading to a pathological state [ 58 ]. Functional CB1 receptor has been shown to be expressed in the human ileum and colon and the number of CB1-expressing cells was found to be significantly increased after inflammation [ 59 , 60 ].
A protective role for these CB1 receptors during inflammation has been shown in a study analyzing the role of the endogenous cannabinoid system in the development of experimental colitis in mice, induced by intrarectal 2,4-dinitrobenzene sulfonic acid DNBS treatment or oral dextran sodium sulfate DSS administration [ 59 ].
The DSS model, originally reported by Okayasu et al. Furthermore, long-term DSS administration produces colorectal carcinoma, which is similar to the dysplasia—carcinoma sequence seen in the course of cancer development in human ulcerative colitis [ 62 ].
The involvement of the endogenous cannabinoid system in the modulation of the acute phase of DNBS-induced colitis was further supported by the increased levels of transcripts coding for CB1 in wild-type mice after induction of inflammation.
It was observed that genetic ablation of CB1 receptors rendered mice more sensitive to inflammatory insults. Furthermore, similar to results observed in CB1-deficient mice, pharmacological blockade of CB1 with the specific antagonist SRA led to a worsening of colitis [ 59 ].
The protective role of the endogenous cannabinoid system was observed 24 h after DNBS treatment and became more evident on days 2 and 3. This gives further support to the notion that the endogenous cannabinoid system is protective against inflammatory changes. These data indicated that the activation of CB1 and the endogenous cannabinoid system is an early and important physiological step in self-protection of the colon against inflammation.
Pharmacological stimulation of cannabinoid receptors with the potent agonist HU also induced a reduction of experimental colitis. It has been reported that cannabinoid receptor stimulation could have a beneficial effect on experimental colitis [ 64 ].
Intraperitoneal application of ACEA, a CB1-selective agonist, and JWH, a CB2-selective agonist, inhibited oil of mustard OM -induced colitis and subsequent symptoms such as induced distal colon weight gain, colon shrinkage, inflammatory damage, diarrhea and histological damage. This study demonstrated a role for CB2 activation in experimental colitis. The fact that both CB1 and CB2 agonists are active in colitis models lends additional support to the theory that signaling through cannabinoid receptors may mediate protective mechanisms in colitis.
In the small intestine, the involvement of CB1 receptors in the control of intestinal motility during croton oil-induced inflammation was recently demonstrated. It was further suggested that increased levels of CB1 receptor expression in inflamed jejuna may contribute to this protective effect. CB1 receptors were shown to modulate gastrointestinal motility during croton oil-induced inflammation in mice.
Fatty acid amide hydrolase is the major enzyme involved in the degradation of several bioactive fatty amides, in particular anandamide [ 11 ], and its genetic deletion in mice leads to a strongly decreased ability to degrade this endocannabinoid and an increase of anandamide levels in several tissues [ 66 ]. In conclusion, cannabinoids have been shown to regulate the tissue response to excessive inflammation in the colon, mediated by both dampening smooth-muscular irritation caused by inflammation and suppressing proinflammatory cytokines, thus controlling the cellular pathways leading to inflammatory responses.
These results strongly suggest that modulation of the physiological activity of the cannabinoid system during colonic inflammation might be a promising therapeutic tool for the treatment of several diseases characterized by inflammation of the GI tract.
During the past few years, awareness of the cannabinoid system in the pathophysiology of liver disease has gained momentum. Many cannabis advocates consider it a miracle medicine , capable of relieving conditions as disparate as depression, arthritis and diabetes. The perception of its widespread medical benefits have made the chemical a rallying cry for legalization advocates. The primary psychoactive ingredient in marijuana is tetrahydrocannabinol THC.
But THC is only one of the scores of chemicals — known as cannabinoids — produced by the cannabis plant. So far, CBD is the most promising compound from both a marketing and a medical perspective. While studies have shown CBD to have anti-inflammatory, anti-pain and anti-psychotic properties , it has seen only minimal testing in human clinical trials, where scientists determine what a drug does, how much patients should take, its side effects and so on.
Despite the government ruling, CBD is widely available over the counter in dispensaries in states where marijuana is legal. The piece, reported by Dr Sanjay Gupta, featured a little girl in Colorado named Charlotte, who had a rare life-threatening form of epilepsy called Dravet syndrome.
What is the Difference Between THC and CBD?
Some patients believe CBD has the most medicinal benefit of all the cannabis compounds. But most of them do not realize that there are. The body of research on cannabidiol, CBD oil benefits, THC, and other . show that cannabis preparations have been used for wound healing in both animals. Hemp CBD oil might be different from cannabis CBD oil, but it's plants are used for a multitude of purposes, not just medicinal or recreational.