It was also found that CBD has a clear anti-stress effect These effects could be associated with the Since CBD can decrease the metabolism/uptake of. It is now clear that CBD has therapeutic potential over a wide range of . Moreover, in this study, it is also possible that CBD could have interfered in . activation of these receptors, possibly by inhibition of anandamide metabolism/ uptake . CBD, a major non-psychoactive constituent of cannabis, has been found to provide . Cannabidiol is also of interest because it can attenuate some D 9 . CBD has anti-anxiety actions , anti-psychotic effects , modulates metabolism of.
therapeutic have also potential? Could metabolites CBD
However, some people are unable to find relief with antidepressant medications alone. CBD interacts with the endocannabinoid system, which has been linked to affects in mood, emotions, and anxiety. Studies suggest that CBD may improve symptoms of depression through actions on this system and other areas in the brain.
People who have added CBD oil to their antidepressant regimen have reported improved symptoms; this is most reported by patients using SSRI medications. That being said, the combination of CBD oil and antidepressants is not taken without risk. CBD has the potential to interact with many antidepressants through the inhibition of their metabolism.
The use of CBD oil in patients on antipsychotic medications is somewhat controversial and is heavily dependent on the cannabis product used and the indication for the antipsychotic medication. The Department of Health has reported that cannabis products are contraindicated, or should not be used, in people with acute psychosis or unstable psychiatric conditions.
This warning may be more applicable for products containing THC, which is the psychoactive cannabinoid found in marijuana plants. CBD oil products do not contain this cannabinoid and do not have psychoactive properties. Products high in CBD have actually been found to potentially reduce symptoms of psychosis. That being said, CBD oil does have the potential to interact with antipsychotic medications.
It has been found to reduce the clearance of some antipsychotic medications from the body. Before using CBD oil with antipsychotics, you should discuss the risks and benefits with your healthcare provider. There are a variety of mood stabilizers used to treat bipolar disorder and supplement treatment for other mental health disorders.
Lithium has been used as a mood stabilizer for decades. There are also many medications that are used as mood stabilizers that are also used in seizure disorders, such as lamotrigine or valproic acid. CBD has been studied in these patients as well, and it has been found to improve mood in bipolar disorder. Some studies have found that CBD may have effects similar to lithium for these patients. Patients who suffer from bipolar disorder may be at higher risk for mood swings if using products containing THC, which can be anxiety-inducing.
CBD also has the potential to interact with these medications through the CYP system in a similar way that it interacts with antidepressants and antipsychotic medications. One patient showed mild improvement, but only slight or no change was observed in the other two, suggesting that CBD may not be effective for the treatment of resistant schizophrenia. Moreover, CBD had no beneficial effects on the performance of schizophrenic patients in the Stroop colour word test, which can be used to assess attentional processes frequently impaired in schizophrenia [ ].
It is still unknown whether chronic administration of CBD could improve the cognitive deficits in the disorder.
No significant side effects were observed during CBD treatment in these clinical studies, suggesting that CBD is safe and well tolerated in schizophrenic patients. In an open-label study evaluating CBD effects on psychotic symptoms associated with L-dopa use in Parkinson's patients [ ], the drug decreased scores of a questionnaire developed to assess psychotic symptoms in Parkinson's disease Parkinson psychosis questionnaire , improved total BPRS scores as well as scores specifically related to positive and negative symptoms.
Confirming the lack of motor effects observed in animal studies, CBD did not affect motor function. On the contrary, it decreased the total scores of the unified Parkinson's disease rating scale, suggesting an improvement of this function.
Overall, therefore, even if there are negative results, most clinical studies with normal subjects or schizophrenic patients suggest that CBD has antipsychotic properties. Corroborating this possibility, a four-week double-blind controlled clinical trial in 42 acute schizophrenic and schizophreniform psychosis patients comparing the effects of CBD with those of amisulpride, an atypical antipsychotic, showed that both treatments were equally effective in reducing acute psychotic symptoms after two and four weeks of treatment [ 34 ].
Moreover, compared with amisulpride, CBD caused a lower incidence of extrapyramidal symptoms and increases in prolactin and weight gain. The presence of antipsychotic properties in CBD is also supported by convergent evidence linking the habitual use of Cannabis to the risk of developing schizophrenia or schizophrenia-like psychosis, especially in vulnerable subjects [ ].
This effect has been attributed to THC. In agreement with the initial reports showing antagonism of THC-induced psychotomimetic effects [ 31 , 87 , 88 ], the presence of CBD in Cannabis strains has been shown to be protective against the occurrence of psychotic-like reactions and cognitive impairment [ — ]. In this context, Di Forti et al. Furthermore, the presence of CBD protects from Cannabis -associated decrease in hippocampal volume [ ]. This finding could reflect a CBD-induced enhancement of neuronal and axonal integrity in these regions [ ].
More recently, Bhattacharyya et al. Few studies in laboratory animals have investigated the possible brain sites and mechanisms of CBD antipsychotic effects. Consistent with the behavioural data described earlier, both CBD and clozapine, but not haloperidol, increased neuronal activation measured by cFos-protein expression in the prefrontal cortex.
Probably reflecting its motor side effects, only haloperidol increased cFos in the dorsal striatum. CBD, and, in addition, increased cFos in the nucleus accumbens [ ], an effect shared by typical and atypical antipsychotic drugs [ ].
Consistent with the behavioural findings in humans and rodents, these drugs caused opposite effects on brain activity in the striatum, anterior cingulate, prefrontal cortex, parahippocampal gyrus, amygdala, right posterior superior temporal gyrus, middle occipital gyrus and cerebellum [ 27 , , , — ]. Behavioural measurements in these studies indicated that some of these changes decreased activation of ventral and dorsal striatum, anterior cingulate gyrus, right temporal lobe are associated with the psychotic-like effects of THC, suggesting that these regions could be possible brain suites of CBD action [ ].
No study using direct injections into key brain regions associated with the pathophysiology of schizophrenia, such as the prefrontal cortex and nucleus accumbens, has been performed so far to investigate CBD antipsychotic properties. Regarding the pharmacological mechanisms, intracerebroventricular administration of CBD enhanced extracellular levels of dopamine in the nucleus accumbens [ ].
A similar finding was found after microdialysis perfusion of CBD 30, 60 or 90 nM into the rat lateral hypothalamus [ ], a procedure that also enhanced alertness. It is unclear how this effect would relate to the antipsychotic properties of CBD because usual antipsychotic drugs act by antagonizing dopamine-2 receptors [ ]. These findings indicate that the mechanisms of CBD effects on glutamate- or dopamine-based models could be at least partially distinct. This possibility needs to be further explored.
Recently, Leweke et al. Moreover, in the CBD group, there was a significant association between anandamide levels and improvement of psychotic symptoms.
However, by indirectly activating CB1 receptors via increased levels of anandamide, CBD could potentially modulate neurotransmitters systems related to these receptors [ , ]. Moreover, as previously discussed, facilitation of CB1-mediated neurotransmission by CBD also increases adult hippocampal neurogenesis, a mechanism that could be related to the cognitive deficits found in schizophrenic patients [ ].
Cannabis sativa exerts significant effects upon humour, which include euphoria and mood elevation [ ].
THC may account for most of these effects through activation of CB1 receptors. Considering these observations, as well as the effects of synthetic cannabinoids and drugs that increase eCB levels, a putative role for the eCB system in mood disorders has been proposed [ ].
The effects of CBD, however, have been scarcely investigated table 4. The fact that this compound, in addition to facilitating eCB activity [ 33 ], may facilitate the activation of 5-HT1A receptors [ 35 ] suggests that it might also have antidepressant-like properties.
Antidepressant-like effects of CBD. Studies with laboratory animals. Stress exposure is a key aetiological factor in depression [ ] and animal models used to study antidepressant-like effects are generally based on acute responses to inescapable aversive stimuli, which are prevented by antidepressants [ ]. Alternatively, considering the nature of depression as a chronic psychiatric disorder, some models investigate drug effects upon the diverse consequences of chronic stress, including anhedonia and changes in exploratory activity [ ].
One of the first studies that indicate the presence of antidepressant-like properties in CBD focused on its ability to prevent the autonomic and behavioural consequences of inescapable stress [ 17 ]. Rats were submitted to restraint stress during 60 min, which increases heart rate and blood pressure and caused anxiogenic-like responses in rats exposed to the elevated plus maze 24 h later.
There were no changes in motor activity or basal cardiovascular parameters, discarding any possible confounding factor [ 17 ]. Similar effects were observed after intra-cisterna magna administration of CBD [ 12 ], thus suggesting that these effects are centrally mediated. Another behavioural model widely used to assess antidepressant-like effects, mainly due to its pharmacological predictability, is the forced swim test.
In this assay, rats or mice exposed to inescapable swimming assume a posture of immobility, which is reversed by antidepressants [ ]. The drug produced an inverted U-shaped dose-response curve.
Our behavioural findings in the forced swimming test were confirmed by another study, published in the same year. The drug had no effect, however, in the mouse tail suspension test. One drawback common to all these studies is that the animals received only acute injections. Depression, however, is a chronic disorder that requires long-lasting drug treatment [ ].
CBD has been recently tested against the consequences of chronic unpredictable stress, which includes anhedonia and anxiety-like behaviour [ ]. Chronic treatment with CBD was able to prevent these behavioural changes, an effect that depends on hippocampal neurogenesis, similar to antidepressant drugs [ 72 ]. This observation further strengthens the notion that this natural cannabinoid should be considered as a potential approach for the treatment of mood disorders.
Despite this body of evidence, no clinical study has investigated whether CBD can decrease depressive symptoms in patients. This compound has been tested, however, in patients suffering from bipolar disorders, a subtype of mood disorder, in whom it was not effective in treating manic episodes [ ].
Actually, this is in line with animal models, in which CBD failed to prevent hyperactivity in rodents [ ]. To summarize, although the data are scarce, preclinical studies so far do provide evidence that this compound could induce antidepressant-like effects. Clinical studies are important to confirm this possibility. Similar to findings with animal models of anxiety, the attenuation of the behavioural consequences of restraint stress and the antidepressant-like effects of CBD in the forced swimming test were attenuated by a 5-HT1A receptor antagonist [ 17 , ].
In the latter model, despite the association between increased expression of neurotrophic factors and antidepressant activity [ ], CBD failed to modify brain-derived neurotrophic factor hippocampal levels [ ]. As discussed earlier, CBD can also facilitate hippocampal neurogenesis, probably by facilitation of eCB neurotransmission [ 72 ].
The involvement of this mechanism on its antidepressant-like properties after repeated administration remains to be investigated. CBD is a safe compound with a wide range of therapeutic applications, including the treatment of psychiatric disorders [ 3 , 4 ]. These findings make this drug an attractive candidate for future clinical use.
Its therapeutic use, however, has some limiting factors. In addition to its low and variable oral bioavailability in humans [ ], it causes bell-shaped dose-response curves and, judging from the studies with laboratory animals, possesses a narrow therapeutic dose range. A clear target of future research, therefore, is to try to develop compounds with similar safety and clinical profile but with larger effective dose ranges.
To this aim, a better understanding of the mechanisms responsible for the unique properties of CBD is essential. The behaviour studies reviewed here clearly indicate that more than one mechanism is involved, depending on the effects being measured anxiolytic, anti-compulsive, antidepressant or antipsychotic-like and the drug regime single versus repeated administration. Facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex, seems responsible for CBD acute anxiolytic-like effects.
Other CBD effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, facilitation of adult hippocampal neurogenesis and blockade of the anxiogenic consequences of chronic unpredictable stress could depend on potentiation of anandamide-mediated neurotransmission. In addition to these mechanisms, CBD can interfere in several other important biological processes e.
Additional in vivo studies are clearly needed to investigate their possible involvement on CBD behavioural effects. National Center for Biotechnology Information , U. Author information Copyright and License information Disclaimer. This article has been cited by other articles in PMC. History Cannabidiol CBD is the main non-psychotropic phytocannabinoid present in the Cannabis sativa plant, constituting up to 40 per cent of its extract.
Cannabidiol and anxiety Early reports describing the effects of CBD in animal models of anxiety were inconsistent. Open in a separate window. Cannabidiol and psychosis Initial studies with laboratory animals suggested that CBD prevents some of the effects produced by THC [ 86 ]. Cannabidiol and depression Cannabis sativa exerts significant effects upon humour, which include euphoria and mood elevation [ ]. Conclusions CBD is a safe compound with a wide range of therapeutic applications, including the treatment of psychiatric disorders [ 3 , 4 ].
Isolation, structure and partial synthesis of an active constituent of hashish. New dawn of cannabinoid pharmacology. Phytocannabinoids as novel therapeutic agents in CNS disorders. Comparative effects between cannabidiol and diazepam on neo-phobia, food intake and conflict behavior. Antianxiety effect of cannabidiol in the elevated plus-maze. Pharmacological characterization of cannabinoids in the elevated plus maze. Anxiolytic- like effect of cannabidiol in the rat Vogel conflict test.
Psychiatry 30 , — Effects of cannabidiol and diazepam on behavioural and cardiovascular responses induced by contextual conditioned fear in rats. Effects of intracisternal administration of cannabidiol on the cardiovascular and behavioral responses to acute restraint stress.
Anti-aversive effects of cannabidiol on innate fear-induced behaviors evoked by an ethological model of panic attacks based on a prey vs the wild snake Epicrates cenchria crassus confrontation paradigm. Neuropsychopharmacology 37 , — Cannabidiol inhibitory effect on marble-burying behaviour: Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM and cannabidiol in conditioned rats.
Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors. Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats.
The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT1A receptors. Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats. Anxiogenic-like effects of chronic cannabidiol administration in rats.
On disruption of fear memory by reconsolidation blockade: Effects of ipsapirone and cannabidiol on human experimental anxiety. Effects of cannabidiol CBD on regional cerebral blood flow. Neuropsychopharmacology 29 , — Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats.
Neuropharmacology 62 , — Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol. Neural basis of anxiolytic effects of cannabidiol CBD in generalized social anxiety disorder: Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology 36 , — This process is generally very complicated. Metabolizing something properly can involve multiple molecular pathways and various enzymes that enable the body to get rid of the compound often done by adding something to the original compound.
These metabolites can have very different properties than the initial drug. Ethanol, for example, owes some of its effects, including much of the hangover, to its two-step metabolism. THC metabolites contribute significantly to the effects of cannabis consumption. Oxidation will usually make a compound more water soluble and therefore easier for the kidneys to filter out.
Both steps in the metabolism of ethanol, mentioned above, and the conversion of THC into OH — THC involve oxidation though ethanol is not oxidized specifically by cytochrome P Different routes of cannabinoid administration have different effects.
Inhaled THC enters capillaries in the lungs, passes into general circulation through the pulmonary arteries, and quickly crosses the blood-brain barrier. The way CBD interacts with cytochrome P is pivotal; in essence, they deactivate each other. The extent to which cannabidiol behaves as a competitive inhibitor of cytochrome P depends on how tightly CBD binds to the active site of the metabolic enzyme before and after oxidation.
If the dosage of cannabidiol is low enough, it will have no noticeable effect on CYP activity, but CBD may still exert other effects. There is no clearly established cut-off dose, below which CBD does not interact with other drugs.
Lester Bornheim, a research pharmacologist at the University of California in San Francisco, was among the first scientists to study the metabolism of CBD. In , he was awarded a NIDA grant to investigate the effects of phytocannabinoids on cytochrome P enzymes.
A year earlier, a team of Canadian scientists identified certain compounds in grapefruit that inhibit the expression of some cytochrome P enzymes—which is why physicians often warn patients not to eat grapefruit before taking their meds.
CBD , it turns out, is a more potent inhibitor of cytochrome P enzymes than the grapefruit compound Bergapten the strongest of several grapefruit components that inhibit CYP s.
The DA Guide to CBD Drug Interactions
A particular focus will be on the therapeutic potential of the phytocannabinoid cannabidiol. Expert opinion: . have confirmed the importance of APOE in AD risk and also. identified .. to lipid metabolism and as such also to vascular disease. diol (CBD)] are produced by the Cannabis sativa plant and. Scientists studying the health benefits of CBD have found it is a promising natural This is also the reason cannabinoids can be used as a general preventative that increases appetite but also increases the metabolism of carbohydrates. in science and suggested they had a broad therapeutic potential for a variety of. As it turns out, CBD has a surprising effect on metabolism. cannabinoid that's non-psychoactive and presents loads of therapeutic potential. but also that CBD can boost the number and activity of mitochondria, magnifying.