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In conclusion, oral administration yielded the most pronounced behavioural effects which corresponded to the highest brain levels of cannabinoids.
Of central importance was the novel finding that THC can be detected in serum and brain after administration of CBD alone which, if confirmed in humans and given the increasing medical use of CBD -only products, might have important legal and forensic ramifications. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis.
Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.
Cannabis contains the psychoactive component delta9-tetrahydrocannabinol delta9-THC , and the non-psychoactive components cannabidiol CBD , cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury.
Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent.
The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Doxorubicin DOX is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity.
Cannabidiol CBD is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. DOX-induced cardiomyopathy was characterized by increased myocardial injury elevated serum creatine kinase and lactate dehydrogenase levels , myocardial oxidative and nitrative stress decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA , myocardial cell death apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent and cardiac dysfunction decline in ejection fraction and left ventricular fractional shortening.
These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may. Beale, Camilla; Broyd, Samantha J. Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus.
This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use.
Participants were assessed at baseline and post- CBD treatment using structural magnetic resonance imaging. Automated longitudinal hippocampal segmentation was performed to assess volumetric change over the whole hippocampus and within 12 subfields. No change was observed in left or right hippocampus as a whole. Heavy cannabis users demonstrated marked growth in the left subicular complex, predominantly within the presubiculum, and right cornu ammonis CA 1 compared to lighter users. Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users.
Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis. While replication is required in a larger, placebo-controlled trial, these findings support a protective role of CBD against. Relevance to Alzheimer's Disease. Microglial activation is an invariant feature of Alzheimer's disease AD. On the other hand, the phytocannabinoid cannabidiol CBD has shown anti-inflammatory properties in different paradigms.
In contrast, 4-[4- 1,1-dimethylheptyl -2,6-dimethoxyphenyl]-6,6-dimethyl-bicyclo[3. All of the cannabinoids decreased lipopolysaccharide-induced nitrite generation, which was insensitive to cannabinoid antagonism. In summary, CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD. Given that CBD lacks psychoactivity, it may represent a novel therapeutic approach for this neurological disease.
The immunosuppressive activity of cannabinoids has been well established. However, the underlying mechanisms are largely unknown. To view the other articles in this section visit http: Safety and side effects of cannabidiol , a Cannabis sativa constituent. Cannabidiol CBD , a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties.
However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", " cannabidiol " and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters heart rate, blood pressure and body temperature , does not affect gastrointestinal transit and does not alter psychomotor or psychological functions.
Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters.
Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects. Cannabidiol CBD is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia.
In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F- CBD HUF 1 , is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol. Aldose reductase ALR2 is a key enzyme involved in diabetic complications and the search for new aldose reductase inhibitors ARIs is currently very important.
The synthetic ARIs are often associated with deleterious side effects and medicinal and edible plants, containing compounds with aldose reductase inhibitory activity, could be useful for prevention and therapy of diabetic complications. Non-psychotropic phytocannabinoids exert multiple pharmacological effects with therapeutic potential in many diseases such as inflammation, cancer, diabetes.
Here, we have investigated the inhibitory effects of extracts and their fractions from two Cannabis sativa L. A molecular docking study was performed to evaluate the interaction of these cannabinoids with the active site of ALR2 compared to known ARIs.
The inhibitory activity of the fractions was greater for acidic cannabinoid-rich fractions. Comparative molecular docking results have shown a higher stability of the ALR2-cannabinoid acids complex than the other inhibitors. These results may have some relevance for the possible use of C. Accumulating evidence suggests that cannabidiol CBD may be an effective and safe anxiolytic agent and potentially also an antidepressant.
The objective of this study was to further examine these properties of CBD using the 'depressive-like' Wistar-Kyoto WKY rat, focusing on the drug's effect on anhedonia-like behaviors. These findings extend the limited knowledge on the antidepressant effect of CBD , now shown for the first time in a genetic animal model of depression. These results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia. Cannabidiol in humans-the quest for therapeutic targets.
Cannabidiol CBD , a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties.
However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients.
Both monotherapy and combination studies e. A total of 34 studies were identified: Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed. Cannabidiol -induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase We recently reported that cannabidiol CBD exhibited a generalized suppressive effect on T-cell functional activities in splenocytes directly exposed to CBD in vitro or isolated from CBD -administered mice.
To investigate the potential mechanisms of CBD effects on T cells, we characterized the pro-apoptotic effect of CBD on primary lymphocytes. The apoptosis of splenocytes was markedly enhanced following CBD exposure in a time- and concentration-dependent manner, as evidenced by nuclear hypodiploidity and DNA strand breaks.
Pretreatment of splenocytes with a cell-permeable inhibitor for caspase-8 significantly attenuated, in a concentration-dependent manner, CBD -mediated apoptosis, but not ROS production. Collectively, the present study demonstrated that the apoptotic effect of CBD in primary lymphocytes is closely associated with oxidative stress-dependent activation of caspase CBD is a constituent of some strains of recreational cannabis but its content is highly variable.
This study was undertaken to determine if CBD could reverse hypothermia or hypolocomotor effects caused by THC in rats. Additional experiments determined the effects of pretreatment with the cannabinoid CB1 receptor antagonist SR rimonabant. CBD did not attentuate THC-induced hypothermia or hypolocomotion but instead exaggerated these effects in some conditions.
There is no evidence from this study that elevated CBD content in cannabis could provide protection from the physiological effects of THC, in rats.
Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: Cannabidiol CBD represents a new promising drug due to a wide spectrum of pharmacological actions. In order to relate CBD clinical efficacy to its pharmacological mechanisms of action, we performed a bibliographic search on PUBMED about all clinical studies investigating the use of CBD as a treatment of psychiatric symptoms. In conclusion, current evidences suggest that CBD has the ability to reduce psychotic, anxiety and withdrawal symptoms by means of several hypothesised pharmacological properties.
However, further studies should include larger randomised controlled samples and investigate the impact of CBD on biological measures in order to correlate CBD 's clinical effects to potential modifications of neurotransmitters signalling and structural and functional cerebral changes.
Cannabidiol as potential treatment in refractory pediatric epilepsy. In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children. From in vitro and in vivo studies on animal models, cannabidiol CBD appears to be a promising anticonvulsant drug with a favorable side-effect profile.
In humans, CBD efficacy and safety is not supported by well-designed trials and its use has been described by anecdotal reports. It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other anti-epileptic drugs AEDs alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.
Does cannabidiol have a role in the treatment of schizophrenia? Schizophrenia is a debilitating psychiatric disorder which places a significant emotional and economic strain on the individual and society-at-large. Unfortunately, currently available therapeutic strategies do not provide adequate relief and some patients are treatment-resistant.
In this regard, cannabidiol CBD , a non-psychoactive constituent of Cannabis sativa, has shown significant promise as a potential antipsychotic for the treatment of schizophrenia.
However, there is still considerable uncertainty about the mechanism of action of CBD as well as the brain regions which are thought to mediate its putative antipsychotic effects. We argue that further research on CBD is required to fast-track its progress to the clinic and in doing so, we may generate novel insights into the neurobiology of schizophrenia. Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: We have recently shown that chronic treatment with cannabidiol CBD was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats.
Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation.
Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms DNM1L and OPA1 , the main integral transmembrane protein of synaptic vesicles synaptophysin , and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats.
We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.
We have previously reported that cannabidiol CBD lowers the incidence of diabetes in young non-obese diabetes-prone NOD female mice. In the present study we show that administration of CBD to 11—14 week old female NOD mice, which are either in a latent diabetes stage or with initial symptoms of diabetes, ameliorates the manifestations of the disease.
In addition, the level of the proinflammatory cytokine IL produced by splenocytes was significantly reduced, whereas the level of the anti-inflammatory IL was significantly elevated following CBD -treatment.
Histological examination of the pancreata of CBD -treated mice revealed more intact islets than in the controls. Our data strengthen our previous assumption that CBD , known to be safe in man, can possibly be used as a therapeutic agent for treatment of type 1 diabetes.
Controlled clinical trial of cannabidiol in Huntington's disease. Based on encouraging preliminary findings, cannabidiol CBD , a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease HD. A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant p greater than 0.
Cannabidiol promotes browning in 3T3-L1 adipocytes. Recruitment of the brown-like phenotype in white adipocytes browning and activation of existing brown adipocytes are currently being investigated as a means to combat obesity. Thus, a wide variety of dietary agents that contribute to browning of white adipocytes have been identified. The present study was designed to investigate the effects of cannabidiol CBD , a major nonpsychotropic phytocannabinoid of Cannabis sativa, on induction of browning in 3T3-L1 adipocytes.
These data suggest possible roles for CBD in browning of white adipocytes, augmentation of lipolysis, thermogenesis, and reduction of lipogenesis. In conclusion, the current data suggest that CBD plays dual modulatory roles in the form of inducing the brown-like phenotype as well as promoting lipid metabolism. Thus, CBD may be explored as a potentially promising therapeutic agent for the prevention of obesity.
The current study examined sex differences in CBD modulation of THC-induced antinociception, hypolocomotion, and metabolism. These results suggest that CBD may enhance THC's antinociceptive and hypolocomotive effects, primarily prolonging THC's duration of action; however, these effects were small and inconsistent across experiments.
Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. In vivo, the effect of CBD BDS was examined on the preneoplastic lesions aberrant crypt foci , polyps and tumours induced by the carcinogenic agent azoxymethane AOM as well as in a xenograft model of colon cancer in mice.
The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients. The cannabis constituent cannabidiol CBD possesses anxiolytic and antipsychotic properties. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations.
Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD , which does not reverse the schizophrenia-relevant phenotypes.
Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice. The surgical technique has evolved since then and several studies have concluded that Laparoscopic common bile duct exploration LCBDE procedures are superior to sequential endolaparoscopic treatment in terms of both clinical and economical outcomes, Cuschieri et al.
Here we present our series from January to March In a retrospective study from January to March , we performed laparoscopic cholecystectomies, out of which patients underwent intraoperative cholangiogram and patients eventually had CBD exploration. Choledochoduodenosotomy was done in 2 patients. Patients were followed regularly at six monthly intervals with a range of six months to three years of follow-up.
There were no major complications like bile leak or pancreatitis. There were no cases of retained stones or intraabdominal infection. Primary closure of choledochotomy in select patients is a. Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation? The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia. Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders.
Of particular interest is the primary nonpsychoactive constituent cannabidiol CBD. Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression. Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.
Cannabidiol CBD is the main non-psychotropic component of the glandular hairs of Cannabis sativa. It displays a plethora of actions including anticonvulsive, sedative, hypnotic, antipsychotic, antiinflammatory and neuroprotective properties. However, it is well established that CBD produces its biological effects without exerting significant intrinsic activity upon cannabinoid receptors.
For this reason, CBD lacks the unwanted psychotropic effects characteristic of marijuana derivatives, so representing one of the bioactive constituents of Cannabis sativa with the highest potential for therapeutic use. The present review reports the pharmacological profile of CBD and summarizes results from preclinical and clinical studies utilizing CBD , alone or in combination with other phytocannabinoids, for the treatment of a number of CNS disorders.
Thapa, Dinesh; Cairns, Elizabeth A. Abstract Background and Purpose: Corneal injury can result in dysfunction of corneal nociceptive signaling and corneal sensitization. Activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory. Gamma-irradiation enhances apoptosis induced by cannabidiol , a non-psychotropic cannabinoid, in cultured HL myeloblastic leukemia cells.
Apoptosis was determined by staining with bisBenzimide and propidium iodide. Human monocytes from normal individuals were resistant to either cannabinoids or gamma-irradiation. Caspase-3 activation was observed after the cannabinoid treatment, and may represent a mechanism for the apoptosis. Our data suggest a possible new approach to treatment of AML. Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Objective To present a summary of current scientific evidence about the cannabinoid, cannabidiol CBD with regards to their relevance to epilepsy and other selected neuropsychiatric disorders.
Methods We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology and data from studies with animal models and human subjects. Results Cannabis has been used to treat disease since ancient times. CBD is anticonvulsant in many acute animal models but there is limited data in chronic models.
CBD has neuroprotective and anti-inflammatory effects. CBD appears to be well tolerated in humans but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD: Significance CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction and neonatal hypoxic-ischemic encephalopathy.
However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with. Clinical experience with THC: CBD oromucosal spray in patients with multiple sclerosis-related spasticity.
Over a month timeframe, THC: CBD spray was initiated in patients. Mean follow-up was 9 months. CBD spray was used as add-on therapy in 95 patients and as monotherapy in 25 patients to achieve best-possible therapeutic results. CBD spray for less than 60 days. Main reasons for treatment discontinuation were: No new safety signals were noted with THC: CBD spray during the evaluation period. CBD spray was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity.
Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine. The information processing appears to be deficient in schizophrenia. Prepulse inhibition PPI , which measures the inhibition of a motor response by a weak sensory event, is considered particularly useful to understand the biology of information processing in schizophrenia patients. Drugs that facilitate dopaminergic neurotransmission such as amphetamine induce PPI disruption in human and rodents.
Clinical and neurobiological findings suggest that the endocannabinoid system and cannabinoids may be implicated in the pathophysiology and treatment of schizophrenia. Cannabidiol CBD , a non-psychotomimetic constituent of the Cannabis sativa plant, has also been reported to have potential as an antipsychotic.
Since one possible mechanism of CBD action is the facilitation of endocannabinoid-mediated neurotransmission through anandamide, we tested the effects of an anandamide hydrolysis inhibitor URB in the amphetamine-induced PPI disruption. Pretreatment with CBD attenuated the amphetamine-disruptive effects on PPI test after systemic or intra-accumbens administration.
Similar effects were also found with the inhibitor of anandamide hydrolysis. These results corroborate findings indicating that CBD induces antipsychotic-like effects. In addition, they pointed to the nucleus accumbens as a possible site of these effects. The increase of anandamide availability may be enrolled in the CBD effects. THC for the treatment of multiple sclerosis. THC dose ratio tested. THC dose ratios of 1: When administered alone, CBD did not produce effects in either procedure.
These results suggest that CBD , when administered with THC at therapeutically relevant ratios, may ameliorate aversive effects e. While this effect may be beneficial for therapeutic usage of a CBD: Cannabidiol reverses the reduction in social interaction produced by low dose Delta 9 -tetrahydrocannabinol in rats.
While Delta 9 -tetrahydrocannabinol THC is the main psychoactive constituent of the cannabis plant, a non-psychoactive constituent is cannabidiol CBD. CBD has been implicated as a potential treatment of a number of disorders including schizophrenia and epilepsy and has been included with THC in a 1: This study investigated the effect of THC and CBD , alone or in combination, on some objective behaviours of rats in the open field.
Pairs of rats were injected with CBD or vehicle followed by THC or vehicle and behaviour in the open field was assessed for 10 min. However, the combination of high dose CBD and high dose THC significantly reduced social interaction between rat pairs, as well as producing a significant decrease in locomotor activity.
Cannabidiol CBD , one of the most abundant Cannabis sativa-derived compounds, has been implicated with neuroprotective effect in several human pathologies. Until now, no undesired side effects have been associated with CBD. In this study, we evaluated CBD 's neuroprotective effect in terminal differentiation mature and during neuronal differentiation neuronal developmental toxicity model of the human neuroblastoma SH-SY5Y cell line.
A dose-response curve was performed to establish a sublethal dose of CBD with antioxidant activity 2. Moreover, no difference in antioxidant potential and neurite density was observed. When SH-SY5Y cells undergoing neuronal differentiation were exposed to CBD , no differences in antioxidant potential and neurite density were observed. However, CBD potentiated the neurotoxicity induced by all redox-active drugs tested. Our data indicate that 2.
Several studies have indicated that CBD displays neurobiological effects, including wake promotion. Moreover, experimental evidence has shown that injections of CBD enhance wake-related compounds, such as monoamines dopamine, serotonin, epinephrine, and norepinephrine.
However, no clear evidence is available regarding the effects of CBD on additional wake-related neurochemicals such as acetylcholine ACh. Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control. This study is the first to show the effects of ACh levels in CBD -treated rats and suggests that the basal forebrain might be a site of action of CBD for wakefulness modulation.
The aim of this study was to compare the patterns of grey and white matter atrophy on MRI in autopsy confirmed progressive supranuclear palsy PSP and corticobasal degeneration CBD , and to determine whether the patterns vary depending on the clinical syndrome. PSP and CBD subjects were also subdivided into those with a dominant dementia or extrapyramidal syndrome.
PSP subjects showed brainstem atrophy with involvement of the cortex and underlying white matter. Frontoparietal grey and subcortical grey matter atrophy occurred in CBD. When subdivided, PSP subjects with an extrapyramidal syndrome had more brainstem atrophy and less cortical atrophy than CBD subjects with an extrapyramidal syndrome.
PSP subjects with a dementia syndrome had more subcortical white matter atrophy than CBD subjects with a dementia syndrome.
Evidence for the efficacy and effectiveness of THC- CBD oromucosal spray in symptom management of patients with spasticity due to multiple sclerosis. This article reviews the current evidence for the efficacy and safety, with dizziness and fatigue as the most common treatment-related adverse events, being mostly mild to moderate in severity. Results from both randomized controlled phase III studies involving about, MS patients or patient-years and recently published studies on everyday clinical practice involving more than patients or more than, patient-years are presented.
The aim of this review is to describe the historical development of research on cannabidiol. After the elucidation of the chemical structure of cannabidiol in , the initial studies showed that cannabidiol was unable to mimic the effects of Cannabis.
In the 's the number of publications on cannabidiol reached a first peak, having the research focused mainly on the interaction with delta9-THC and its antiepileptic and sedative effects. The following two decades showed lower degree of interest, and the potential therapeutic properties of cannabidiol investigated were mainly the anxiolytic, antipsychotic and on motor diseases effects.
The last five years have shown a remarkable increase in publications on cannabidiol mainly stimulated by the discovery of its anti-inflammatory, anti-oxidative and neuroprotective effects. These studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson's disease, Alzheimer's disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer.
In the last 45 years it has been possible to demonstrate that CBD has a wide range of pharmacological effects, many of which being of great therapeutic interest, but still waiting to be confirmed by clinical trials. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. The endocannabinoid system ECS regulates multiple physiological processes, including cutaneous cell growth and differentiation.
Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, - - cannabidiol CBD , on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 TRPV4 ion channels.
Animal and humans studies suggest that the two main constituents of cannabis sativa, deltatetrahydrocannabinol THC and cannabidiol CBD have quite different acute effects. However, to date the two compounds have largely been studied separately. A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration.
The area under the curve AUC between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition THC or CBD or placebo as the factor.
Relative to both placebo and CBD , administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication AUC and effect at 2 hours: In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated. Although it is known that these hydrophobic compounds can be transported in blood by albumin or lipoproteins, the intracellular carrier has not been identified.
Recent reports suggest that CBD and THC elevate the levels of the endocannabinoid anandamide AEA when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance.
Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD. Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids.
These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy toward epilepsy and other neurological disorders. Cannabis contains a number of phytocannabinoids in addition to THC , one of which, cannabidiol CBD , has been reported to antagonize some of the aversive effects of THC.
Consistent with previous research, THC self-administration was modest and only evident in a subset of animals and unaffected by sex. Cocaine self-administration was high and evident in the majority of animals tested, indicating that the design was sensitive to drug reinforcement.
Future developments of animal models of THC self-administration and the examination of factors that affect its display remain important to establish procedures designed to assess the basis for and treatment of cannabis use and abuse. Randomized, double-blind, placebo-controlled study about the effects of cannabidiol CBD on the pharmacokinetics of Delta9-tetrahydrocannabinol THC after oral application of THC verses standardized cannabis extract.
As a reason, pharmacodynamic as well as pharmacokinetic mechanisms were suggested. Blood samples were taken 30 minutes before and 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours and 24 hours after the intake. The concentration versus time curves maximum concentrations Cmax, corresponding time tmax and areas under the curves AUC were evaluated by statistical methods with respect to equivalence or differences between the CAN-set and the THC -set.
The probability for this inhibition is particularly high for oral intake because THC and CBD attain relatively high concentrations in the liver and because of the high first-pass metabolism of THC. However, the effect of CBD is small in comparison to the variability caused by other factors. Therefore, a pharmacokinetic reason for the differences determined between pure THC and cannabis extract is improbable at. Several publications have suggested increasing cannabis potency over the last decade, which, together with lower amounts of cannabidiol CBD , could contribute to an increase in adverse effects after cannabis smoking.
This study aimed to investigate the relationship between THC - and CBD concentrations in blood samples among cannabis users, and to compare cannabinoid concentrations with the outcome of a clinical test of impairment CTI and between traffic accidents and non-accident driving under the influence of drugs DUID -cases.
Seizure sample analysis did not reveal high potency cannabis products, and while CBD content appeared high in hashish, it was almost absent in marijuana. Therefore we investigated, in Wistar rats, effects of pulmonary, oral and subcutaneous sc. While cannabinoid serum and brain levels rapidly peaked and diminished after pulmonary administration, sc. In contrast, oral CBD produced mild hyperlocomotion. In conclusion, oral administration yielded the most pronounced behavioural effects which corresponded to the highest brain levels of cannabinoids.
Of central importance was the novel finding that THC can be detected in serum and brain after administration of CBD alone which, if confirmed in humans and given the increasing medical use of CBD -only products, might have important legal and forensic ramifications. The PNL is composed of lipid and emulsifying excipients of GRAS status and are known to increase solubility and reduce Phase I metabolism of lipophilic active compounds.
These molecules are natural alkaloids and phenolic compounds which were reported to inhibit certain phase I and phase II metabolism processes. Here we use piperine, curcumin and resveratrol to formulate the Advanced-PNL formulations.
This co-localization provides an increase in CBD and THC bioavailability by its effect at the pre-enterocyte and the enterocyte levels of the absorption process. These novel results pave the way to utilize piperine-PNL delivery system for other poorly soluble, highly metabolized. This method also involved the optimization of cannabinoids and their metabolites extraction in order to remove co-eluting phospholipids and increase the sensitivity of the MS detection.
After oral administration, the amount of CBD dissolved in olive oil was higher than that absorbed from an ethanolic solution. This could be explained by the protection of lipid excipients towards CBD from acidic gastric juice. GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [ THC: The cannabis for this programme is grown in a secret location in the UK.
It is expected that the product will be marketed in the US in late The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled but not smoked dosage forms. The technology is protected by patent applications.
GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines. GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines.
The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets. GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK.
The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: Clinical experience with THC: CBD oromucosal spray in patients with multiple sclerosis-related spasticity.
Over a month timeframe, THC: CBD spray was initiated in patients. Mean follow-up was 9 months. CBD spray was used as add-on therapy in 95 patients and as monotherapy in 25 patients to achieve best-possible therapeutic results.
CBD spray for less than 60 days. Main reasons for treatment discontinuation were: No new safety signals were noted with THC: CBD spray during the evaluation period. CBD spray was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity.
Cannabinoid receptors in the brain CB 1 take part in modulation of learning, and are particularly important for working and short-term memory. Here, we employed a delayed-matching-to-place DMTP task in the open-field water maze and examined the effects of cannabis plant extracts rich in either Delta 9 -tetrahydrocannabinol Delta 9 - THC , or rich in cannabidiol CBD , on spatial working and short-term memory formation in rats.
Delta 9 - THC -rich extracts impaired performance in the memory trial trial 2 of the DMTP task in a dose-dependent but delay-independent manner. CBD potentiated an inhibition of body weight gain caused by chronic THC , and mildly augmented the anxiogenic effects, locomotor suppressant effects and decreased social interaction seen with THC. CBD can potentiate the psychoactive and physiological effects of THC in rats, most likely by delaying the metabolism and elimination of THC through an action on the CYP enzymes that metabolise both drugs.
Interactions between THC and cannabidiol in mouse models of cannabinoid activity. Interest persists in characterizing potential interactions between Delta 9 -tetrahydocannabinol THC and other marijuana constituents such as cannabidiol CBD.
Such interactions may have important implications for understanding the long-term health consequences of chronic marijuana use as well as for attempts to develop therapeutic uses for THC and other CB 1 agonists.
We investigated whether CBD may modulate the pharmacological effects of intravenously administered THC or inhaled marijuana smoke on hypoactivity, antinociception, catalepsy, and hypothermia, the well characterized models of cannabinoid activity.
As the amount of CBD found in most marijuana strains in the US is considerably less than that of THC , these results suggest that CBD concentrations relevant to what is normally found in marijuana exert very little, if any, modulatory effects on CB 1 -receptor-mediated pharmacological effects of marijuana smoke.
Alzheimer's disease AD is a debilitating neurodegenerative disease that is affecting an increasing number of people. Current AD treatments do not stop or reverse the disease progression, highlighting the need for new, more effective therapeutics.
Cannabidiol CBD is a non-psychoactive phytocannabinoid that has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro. Thus, it is investigated as a potential multifunctional treatment option for AD. Here, we summarize the current status quo of in vivo effects of CBD in established pharmacological and transgenic animal models for AD.
The studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models. Further investigations should address the long-term potential of CBD and evaluate mechanisms involved in the therapeutic effects described.
There was evidence of dose-proportionality in the single but not the multiple dosing data sets. The bioavailability of THC was greater than CBD at single and multiple doses, and there was no evidence of accumulation for any analyte with multiple dosing. Inter-subject variability ranged from moderate to high for all PK parameters in this study. The time to peak plasma concentration Tmax was longest for all analytes in the eight spray group, but was similar in the two and four spray groups.
Deuterated d3 internal standards were added to 1-mL samples. Preparation involved acetonitrile precipitation, liquid-liquid extraction hexane: Selected reaction monitoring was employed. Blood samples were provided from a marijuana smoking study two participants and a CBD ingestion study eight participants. Preparation involved acetonitrile precipitation, liquid—liquid extraction hexane: Cannabidiol inhibits THC -elicited paranoid symptoms and hippocampal-dependent memory impairment.
Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC -elicited psychosis and cognitive impairment. Previous studies report sex differences in some, but not all, responses to cannabinoids in rats. The majority of studies use parenteral injection; however, most human use is via smoke inhalation and, increasingly, vapor inhalation.
Male and female Wistar rats were implanted with radiotelemetry devices for the assessment of body temperature and locomotor activity. THC dose was adjusted via the concentration in the vehicle Anti-nociception was evaluated using a tail-withdrawal assay following vapor inhalation.
Plasma samples obtained following inhalation in different groups of rats were compared for THC content. THC inhalation reduced body temperature and increased tail-withdrawal latency in both sexes equivalently and in a concentration-dependent manner. Female temperature, activity, and tail-withdrawal responses to THC did not differ between estrus and diestrus.
CBD inhalation alone induced modest hypothermia and suppressed locomotor activity in both males and females. In summary, the inhalation of THC or CBD , alone and in combination, produces approximately equivalent effects in male and female rats. This confirms the efficacy of the e-cigarette-based method of THC delivery in female rats.
Besides the psychoactive Delta 9 -tetrahydrocannabinol THC , hashish and marijuana as well as cannabis-based medicine extracts contain varying amounts of cannabidiol CBD and of the degradation product cannabinol CBN.
The additional determination of these compounds is interesting from forensic and medical points of view because it can be used for further proof of cannabis exposure and because CBD is known to modify the effects of THC. The limits of detection were between 0. The method was applied in a prospective pharmacokinetic study after single oral administration of 10 mg THC alone or together with 5.
The maximum plasma concentrations after cannabis extract administration ranged between 1. CBN was not detected. Caused by the strong first-pass metabolism, the concentrations of the metabolites were increased during the first hours after drug administration when compared to literature data for smoking. CBD spray and MS spasticity symptoms: A randomized, placebo controlled long-term follow-up clinical trial with THC: CBD spray versus placebo demonstrated that it was not associated with cognitive decline, depression or significant mood changes after 12 months of treatment.
CBD oromucosal spray did not adversely influence standard driving ability in patients with moderate to severe MS spasticity. Other new long term observational data about the use of THC: Findings to date reinforce the efficacy and safety observed in Phase III clinical trials. It is of interest that in practice average dosages used by patients tended to be lower than those reported in clinical studies Thus, these new data support a positive benefit-risk relationship for THC: CBD oromucosal spray during longer-term use.
Rebound hyperactivity, sensorimotor gating and epigenetic and neuroadaptive changes in the mesolimbic pathway. While there is abundant data on acute interactions between CBD and THC , few studies have assessed the impact of their repeated co-administration. We previously reported that CBD inhibited or potentiated the acute effects of THC dependent on the measure being examined at a 1: Here we extend on these finding by examining over 15 days of treatment whether CBD modulated the repeated effects of THC on behaviour and neuroadaption markers in the mesolimbic dopamine pathway.
After acute locomotor suppression, repeated THC caused rebound locomotor hyperactivity that was modestly inhibited by CBD. These subtle effects were found at a 1: THC dose ratio but were not accentuated by a 5: These changes suggest that while CBD may have protective effects acutely, its long-term molecular actions on the brain are more complex and may be supradditive. Plant material was dried, homogenized and extracted with methanol by ultrasonication. Analytes were detected and quantified using a Waters photo diode array detector.
Since no thermal decarboxylation of THCA-A occurs, the method is highly reproducible for different cannabis materials. Published by Elsevier Ireland Ltd. The influence of THC: CBD oromucosal spray on driving ability in patients with multiple sclerosis-related spasticity. Driving ability is a key function for the majority of patients with multiple sclerosis MS to help maintain daily interactions. Both physical and cognitive disability, as well as treatments, may affect the ability to drive.
Spasticity is a common symptom associated with MS, and it may affect driving performance either directly or via the medications used to treat it. The articles identified using these search terms were augmented with relevant references from these papers and other articles known to the authors.
The results from THC: CBD oromucosal spray driving studies and real-world registries did not show any evidence of an increase in motor vehicle accidents associated with THC: The majority of patients reported an improvement in driving ability after starting THC: It should be noted that THC blood levels are significantly lower than the levels associated with recreational use of herbal cannabis.
CBD oromucosal spray was shown not to impair driving performance. However, periodic assessment of patients with MS driving ability is recommended, especially after relapses and changes in treatment. CBD oromucosal spray, thus specific knowledge of each country's driving regulations and a medical certificate are recommended. Twenty-one MS patients were screened, and 15 cases have been evaluated. A complete neurological evaluation, including the assessment of their spasticity using the Modified Ashworth Scale MAS and the spasticity numerical rating scale NRS , was performed at the same times.
Mobility was evaluated through the ft walking-time test TWT. When coadministered in a 1: When co-administered in a 1: The legal status of cannabis marijuana and cannabidiol CBD under U. In the United States, federal and state laws regarding the medical use of cannabis and cannabinoids are in conflict and have led to confusion among patients, caregivers, and healthcare providers. Many of these artisanal products are sold in dispensaries or over the internet. Understanding how federal laws apply to clinical research and practice can be challenging, and the complexity of these laws has resulted in particular confusion regarding the legal status of CBD.
This paper provides an up-to-date overview as of August of the legal aspects of cannabis and cannabidiol , including cultivation, manufacture, distribution, and use for medical purposes. This article is part of a Special Issue title, Cannabinoids and Epilepsy. Published by Elsevier Inc. Who benefits most from THC: Learning from clinical experience.
Consequently, detailed experience with individual patients is important to provide examples of therapy to specific patient types. In this article, real-life data from clinical practice showing specific aspects relating to use of 9-delta-tetrahydocannabinol and cannabidiol THC: Three common clinical scenarios will be considered: These case reports highlight the diverse nature of the MS spasticity population and they show the possible usefulness of THC: CBD oromucosal spray in individual patients with moderate to severe spasticity resistant to existing therapies, within the frame of use approved after large clinical trial results.
There was no indication of any effect on heart rate, atrioventricular conduction, or cardiac depolarization and no new clinically relevant morphological changes were observed. Overall, 19 subjects Peripheral neuropathic pain PNP associated with allodynia poses a significant clinical challenge. Various key secondary measures of pain and functioning were also investigated. Full Remission after Switching to Purified Cannabidiol.
Animal studies and preliminary clinical trials have shown that cannabidiol CBD -enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy Case A with left frontal dysplasia and Case B with Dravet Syndrome with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time.
These cases support pre-clinical and preliminary clinical evidence suggesting that CBD may be effective for some patients with epilepsy. Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines.
Cannabidiol CBD and its analogs: Subsequent studies resulted in the pronouncement that THC was the 'active' principle of Cannabis and research then focused primarily on it to the virtual exclusion of CBD. In retrospect this must be seen as unfortunate since a number of actions of CBD with potential therapeutic benefit were downplayed for many years.
In this review, attention will be focused on the effects of CBD in the broad area of inflammation where such benefits seem likely to be developed. Validation of a two-dimensional gas chromatography mass spectrometry method for the simultaneous quantification of cannabidiol , Delta 9 -tetrahydrocannabinol THC , hydroxy- THC , and norcarboxy- THC in plasma.
The lower calibration curve was linear from 0. This procedure prevented laborious re-extraction by allowing the same specimen to be re-injected for quantification on the high calibration curve. Analytes were stable when stored at 22 degrees C for 16 h, 4 degrees C for 48 h, after three freeze-thaw cycles at degrees C and when stored on the autosampler for 48 h.
This sensitive and specific 2D-GCMS assay provides a new means of simultaneously quantifying CBD , THC and metabolite biomarkers in clinical medicine, forensic toxicology, workplace drug testing, and driving under the influence of drugs programs.
Ketoprofen was added to hair samples as internal standard for the other compounds. Responses were linear ranging from 0. The intra-assay precisions ranged from THC , The analytical method was applied to 87 human hair samples, obtained from individuals who testified in court of having committed drug related crimes.
The latter may give rise. Thirty-six healthy male subjects were divided into three groups of 12, and then randomized to one of two treatment sequences per group.
Cmax reduced from 2. Statistically significant increases in the mean area under the curve AUC and mean maximum plasma drug concentration Cmax were observed in subjects during fed conditions.
A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects 4. Food also appeared to delay the time to peak concentration Tmax of all analytes by approximately Only mild adverse events were reported. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant. Comment on Merrick et al. Cannabis and Cannabinoid Research ;1 1: Abstract This short communication examines the question whether the experimental data presented in a study by Merrick et al.
These authors found that cannabidiol CBD , a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta THC and delta THC to a relevant degree. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC.
On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. Thus, there is no reason to avoid oral use of CBD , which has been demonstrated to be a safe means of administration of CBD , even at very high doses.
Thapa, Dinesh; Cairns, Elizabeth A. Abstract Background and Purpose: Corneal injury can result in dysfunction of corneal nociceptive signaling and corneal sensitization. Activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory.
The drug has also recently been registered by the Therapeutic Goods Administration TGA in Australia for treatment of multiple sclerosis. The study was a double-blind, placebo controlled design. The low dose contained 5. Chronic pain in patients with advanced cancer poses a serious clinical challenge. The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease i.
Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.
Cancer Pain Relief Committee. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: This study compared the efficacy of a tetrahydrocannabinol: CBD extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer.
In total, patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, entered a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Patients were randomized to THC: CBD compared with placebo improvement of Twice as many patients taking THC: There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups.
No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment. This study shows that THC: CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.
To determine, via narrative, non-systematic review of pre-clinical and clinical studies, whether the effect of cannabis on hepatic biotransformation pathways would be predicted to result in clinically significant drug-drug interactions DDIs with commonly prescribed psychotropic agents.
A non-systematic literature search was conducted using the following databases: The search term cannabis was cross-referenced with the terms drug interactions, cytochrome, cannabinoids, cannabidiol , and medical marijuana.
Bibliographies were also manually searched for additional citations that were relevant to the overarching aim of this paper. CBD in Daily Practice: From the time Sativex THC: CBD oromucosal spray first became available in European Union countries in for the management of treatment-resistant multiple sclerosis MS spasticity, data from daily practice have been collected through various projects.
A retrospective registry study and a prospective safety study of THC: CBD oromucosal spray are reported. The most recent analysis of a retrospective registry established in the United Kingdom UK , Germany and Switzerland, which collected safety data on more than patients, has indicated a positive risk-benefit profile for THC: CBD oromucosal spray during long-term use.
No new safety concerns were identified, and adverse events of special interest for a cannabis-based medicine were limited. The UK registry has since been closed but remains open in Germany and Switzerland. A prospective safety study undertaken in Spain involved patients from 13 specialized MS centres who had been prescribed THC: The homogeneity between these observational studies supports the interest in THC: CBD oromucosal spray for management of MS spasticity in daily practice.
Palatability and oral cavity tolerability of THC: CBD oromucosal spray and possible improvement measures in multiple sclerosis patients with resistant spasticity: CBD oromucosal spray to mitigate these effects.
Patient comfort, satisfaction and treatment adherence may benefit from these interventions. A Multicenter Randomized Controlled Trial. Research in both animals and humans indicates that cannabidiol CBD has antipsychotic properties.
The authors assessed the safety and effectiveness of CBD in patients with schizophrenia. In an exploratory double-blind parallel-group trial, patients with schizophrenia were randomized in a 1: These findings suggest that CBD has beneficial effects in patients with schizophrenia.
As CBD 's effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder. Many effects of the non-psychoactive cannabinoid, cannabidiol CBD , have been described in immune responses induced by strong immunological stimuli.
Cannabidiol CBD is a plant-derived cannabinoid that has been predominantly characterized as anti-inflammatory. However, it is clear that immune effects of cannabinoids can vary with cannabinoid concentration, or type or magnitude of immune stimulus. The enhanced inflammatory cell infiltrate as observed in bronchoalveolar lavage fluid BALF was comprised mainly of neutrophils, with some monocytes.
These results demonstrate that the CBD -mediated enhancement of LPS-induced pulmonary inflammation is mediated at the level of transcription of a variety of pro-inflammatory genes. The significance of these studies is that CBD is part of a therapeutic currently in use for spasticity and pain in multiple sclerosis patients, and therefore it is important to further understand mechanisms by which CBD alters immune function.
CBD , nabiximols oromucosal spray. An observational registry to collect safety data from patients receiving THC: CBD was set up following its approval in the UK, Germany, and Switzerland, with the aim of determining its long-term safety in clinical practice.
CBD , clinically significant adverse events AEs , and special interest events. The Registry contains data from patients with 2, Thirty-two percent of patients stopped treatment, with approximately one third citing lack of effectiveness and one quarter citing AEs.
AEs were more common during the first month of treatment. The most common treatment-related AEs included dizziness 2. There were no signals to indicate abuse, diversion, or dependence. The long-term risk profile from the Registry is consistent with the known labeled safety profile of THC: CBD , and therefore supports it being a well-tolerated and beneficial medication for the treatment of MS spasticity.
No evidence of new long-term safety concerns has emerged. Twice a year, the Registry was opened to prescribing physicians to voluntarily report data on patients' use of THC: Interest in the potential therapeutic effects of CBD has been growing rapidly, partially in response to media attention surrounding the use of CBD oil in young children with intractable seizure disorders including Dravet syndrome and Lennox-Gastaut syndrome.
While there are promising preliminary data, the scientific literature is currently insufficient to either prove or disprove the efficacy and safety of CBD in patients with epilepsy. In addition to epilepsy, the therapeutic potential of CBD is currently being explored for a number of indications including anxiety disorders, substance use disorders, schizophrenia, cancer, pain, inflammatory diseases and others.
My testimony will provide an overview of what the science tells us about the therapeutic potential of CBD and of the ongoing research supported by NIH in this area. It has not been approved in the United States, but clinical trials are ongoing, and two recent studies reported that nabiximols reduced the severity of spasticity in MS patients. However, the current evidence suggests that the analgesia is mediated by THC and it is unclear whether CBD contributes to the therapeutic effects.
However, the anti-inflammatory properties of CBD discussed above could be predicted to play a role in the analgesic effects of nabiximols. Recent research has also suggested that cannabinoids and opioids have different mechanisms for reducing pain and that their effects may be additive, which suggests that combination therapies may be developed that may have reduced risks compared to current opioid therapies.
However, this work is very preliminary. There are multiple industry sponsored clinical trials underway to begin to test the efficacy of CBD in human cancer patients. Anti-Psychotic Effects Marijuana can produce acute psychotic episodes at high doses, and several studies have linked marijuana use to increased risk for chronic psychosis in individuals with specific genetic risk factors.
Research suggests that these effects are mediated by THC, and it has been suggested that CBD may mitigate these effects. Three weeks ago I had the opportunity to testify before the Senate on cannabidiol, or CBD — one of the main active ingredients in the Anti-Anxiety Effects CBD has shown therapeutic efficacy in a range of animal models of anxiety and stress, reducing both behavioral and physiological e.
CBD reduced anxiety in patients with social anxiety subjected to a stressful public speaking task. CBD reduced the rewarding effects of morphinexxxviii and reduced cue-induced heroin seekingxxxix in animal models. NIDA is supporting multiple ongoing clinical trials in this area. Research Opportunities and Challenges This is a critical area for new research.
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