Information about the use of cannabis oil for epilepsy to gain seizure control. The most well known are two cannabinoids: CBD - cannabidiol - and THC does not respond to conventional licensed anti-epileptic medications. This study showed that the addition of CBD to a traditional seizure medication decreased the frequency of drop seizures significantly in children and adults with . Nearly 30% of epileptic patients are resistant to traditional anticonvulsant drug treatments, making the use of alternative treatments such as.
& CBD Epilepsy, conventional medicine
Studies were generally retrospective, and based on patient or parenteral reports without adequately structured data collection. Many of the patients surveyed used unspecified products whose composition and dosage was unknown.
An indication that patient or parental expectations may have a strong impact on the outcome of cannabis treatment is provided by a comparison of perceived improvement among patients included in the Colorado surveys.
To date, the largest exploratory study of the tolerability and anti-seizure activity of CBD relates to a recent physician-sponsored expanded-access programme at 11 epilepsy centres in the USA. Tolerability and safety were analysed for the group of patients who achieved at least 12 weeks of follow-up—this included 33 patients with Dravet syndrome and 31 patients with Lennox-Gastaut syndrome.
Patients on clobazam, however, were also more likely to develop adverse effects, particularly somnolence and fatigue. These differences in outcome in relation to type of comedication may be explained by the increase in plasma clobazam and N-desmethyl-clobazam levels caused by CBD.
Overall, the main value of these studies is in providing a preliminary characterization of CBD safety profile. Data concerning improvement in seizure control, however, are difficult to assess in view of the uncontrolled nature of the observations. Smaller uncontrolled studies and case reports have also suggested that CBD could be of value in the treatment of patients with drug resistant seizures associated with tuberous sclerosis complex, , febrile infection-related epilepsy syndrome FIRES , Sturge-Weber syndrome and malignant migrating partial seizures in infancy.
The recent flurry of research focused on the potential usefulness of cannabinoids in epilepsy has resulted in the completion of three well controlled randomized trials, all of which evaluated a liquid proprietary oral formulation of CBD.
As an indication of the high interest of the medical community in the application of cannabinoids to epilepsy management, the first randomized placebo-controlled double-blind trial of CBD in Dravet syndrome was published in the New England Journal of Medicine in May The duration of treatment was 14 weeks, including a 2-week-titration phase.
Compared with baseline, the median monthly frequency of convulsive seizures defined as the sum of tonic-clonic, tonic, clonic, and atonic seizures decreased from Median percent changes in seizure frequency are shown in Fig.
Non-convulsive seizures were not significantly affected by CBD therapy. Median percent reduction in seizure frequency in the three randomized adjunctive-therapy placebo-controlled efficacy trials of cannabidiol CBD reported to date in patients with Dravet syndrome 85 and Lennox-Gastaut syndrome.
For patients with Lennox-Gastaut syndrome, seizure frequency refers to drop seizures. P values refer to comparisons between each CBD group and corresponding placebo group. For further details, see text. Somnolence, diarrhea, and decreased appetite were the most common CBD-associated adverse events Table 2. Eighteen of the 22 CBD-treated patients who developed somnolence were on clobazam comedication.
Adverse events appeared mostly during the first two weeks of therapy, and there were instances in which the dose of CBD or other medications were reduced. No information, however, was reported on how often the dose of concomitant clobazam was reduced. Eight patients in the CBD group discontinued the trial prematurely due to adverse events in three cases, marked elevation of liver enzymes , compared with one patient in the placebo group who also had a marked elevation in liver enzymes.
Overall, elevated aminotransferases levels occurred in 12 patients in the CBD group and one in the placebo group, all of whom were on concomitant valproate therapy. In the nine patients with raised aminotransferases who did not discontinued treatment, liver enzymes reverted to normal on continuation of therapy. Adverse events most commonly reported in the randomized double-bind placebo-controlled trial of CBD in comparison with placebo in patients with Dravet syndrome Overall, this trial provides for the first time robust evidence that CBD added-on to pre-existing AED treatment reduces the frequency of convulsive seizures in children and young adults with Dravet syndrome.
Interestingly, no significant differences between groups were found in sleep scores, behavioral adaptation Vineland-II scores, and Quality of Life in Childhood Epilepsy scores, even though duration of treatment was relatively short and possibly insufficient to determine changes in these parameters.
A major weakness in the presentation of the trial results is the failure to report changes in plasma concentrations of concomitant AEDs and, most notably, clobazam and N-desmethylclobazam. Two well controlled double-blind trials in patients with Lennox-Gastaut syndrome have been completed, but results to date have only been reported in summary form.
Treatment-related serious adverse events were reported in nine CBD patients and one placebo patient.
Elevations in transaminases occurred mostly in patients on concomitant valproate therapy and all resolved. Duration of the trial was 14 weeks 2-week titration and week maintenance.
Total seizures were also significantly reduced in both CBD groups compared with placebo. Some elevations in transaminases were seen. Published reports, however, provide no information on concomitant therapies, and most notably whether, and to what extent, the clinical improvement on CBD therapy could be related to elevation in serum concentrations of other medications, most notably clobazam and N-desmethylclobazam.
The interest in cannabis preparations in the treatment of epilepsies, particularly drug refractory childhood epilepsies, has skyrocketed in recent years. Marijuana and other cannabis products with moderate to high THC content utilized primarily for recreational purposes are generally unsuitable for this indication, not only because evidence for an anti-seizure activity of THC is equivocal and risk of seizure aggravation cannot be excluded, but also because THC is associated with many undesired effects, including addiction liability, psychiatric disorders, cognitive and motor impairment — and, possibly, also cardiovascular toxicity.
Compared with THC, CBD shows a better defined anticonvulsant profile in animal models considered to be predictive of efficacy against focal and generalized seizures.
Moreover, CBD is largely devoid of adverse psychoactive effects, and is considered to lack the abuse liability associated with THC-containing products. Improvement in seizure control, often associated with additional benefits on sleep and behaviour, have been reported in a sizeable proportion of cases, 87 but interpretation of these data is made difficult by the uncontrolled nature of the observations. Additionally, as discussed in this article, there are concerns about the quality and variability of many of the products used, 98 particularly because cannabis treatment is often initiated spontaneously by patients or caregivers without adequate medical supervision.
Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a turning point in the last 12 months, with the completion of the first high-quality placebo-controlled trials of a purified oil-based liquid CBD preparation in patients with Dravet syndrome and Lennox-Gastaut syndrome. Therefore there is now for the first time class 1 evidence that CBD improves seizure control when added on to other AEDs in patients with two difficult-to-treat epileptic encephalopathies.
Available data, however, do not allow to conclude that CBD per se has anti-seizure activity. At least for the trial published in full, 85 a majority of patients were receiving concomitant clobazam therapy, and it is unclear whether the reported seizure benefits, as well as adverse effects, were related to a direct action of CBD, or were mediated by a previously described 5-fold elevation in plasma N-desmethylclobazam levels. For the two studies in Lennox-Gastaut syndrome, the proportion of patients on concomitant clobazam therapy was not reported, but it is likely to have been significant because clobazam is a frequently used comedication in patients with this syndrome.
Clarification of the independent effects of CBD would require re-assessment of trial data for the subgroup of patients not comedicated with clobazam, or the conduction of further studies after excluding such patients or, alternatively, adjusting blindly clobazam dosages to maintain unaltered concentration of N-desmethylclobazam. Additional well controlled studies are also desirable to determine the potential value of CBD in other seizure types and epilepsy syndromes, including refractory focal epilepsies.
One of the reasons for the utilization of cannabis products to have become so popular among patients and their caregivers is that these products are generally regarded as causing fewer adverse effects compared with traditional AEDs, partly out of the misperception that remedies derived from natural products are unlikely to be harmful.
Although these results are encouraging, further studies are required to evaluate the safety profile of CBD and other cannabis products in greater detail, particularly after long-term exposure and whenever these products are used in subpopulations potentially at risk. Elevations of liver enzymes have been frequently observed, especially in patients comedicated with valproate, and although they were generally reversible, close observation for signs suggestive of hepatic toxicity is advisable.
Nabiximols, an oromucosal spray formulation containing approximately equal amounts of THC and CBD, has been commercially available in several countries for a number of years and has a relatively extensive safety record. Unlike THC, CBD is not associated with the development of tolerance after repeated administration in various seizure models, and there is no evidence of a withdrawal syndrome developing after CBD discontinuation. These are exciting times for research in cannabinoids. After almost four millennia of their documented medical use in the treatment of seizure disorders, we are very close to obtaining conclusive evidence of their efficacy in some severe epilepsy syndromes.
The era of evidence-based prescription of a cannabis product is within our sight. National Center for Biotechnology Information , U. Journal List J Epilepsy Res v. Published online Dec Emilio Perucca 1, 2. Author information Article notes Copyright and License information Disclaimer. Received Jul 11; Accepted Sep This article has been cited by other articles in PMC. Abstract The interest in cannabis-based products for the treatment of refractory epilepsy has skyrocketed in recent years.
Cannabis, Cannabidiol, Epilepsy, Seizures, Review. Introduction The history of human use of the Cannabis plant goes back to the dawn of mankind. Open in a separate window. Chemistry and mechanisms of action The genus Cannabis refers to a flowering plant of which there are three main species, Cannabis sativa , Cannabis indica and Cannabis ruderalis.
Table 1 A list of targets and actions reported for CBD based on results of studies in different experimental models and systems 24 — Pharmacological profile in experimental models of seizures and epilepsy Among the many active principles found in the cannabis plant, THC is the most widely investigated for its many actions, including its psychoactive effects and risks associated with overdose and abuse.
CBD In preclinical studies, CBD has been found to be active in a variety of seizures models, including seizures induced by maximal electro-shock 39 — 41 and by pentylentetrazole in rats and mice, 42 — 44 audiogenic seizures in rats 45 and seizures induced by 3-mercaptopropionic acid, bicuculline, picrotoxin, cocaine and isoniazid but not strychnine in mice.
Clinical evidence of efficacy and safety: Well controlled randomized trials The recent flurry of research focused on the potential usefulness of cannabinoids in epilepsy has resulted in the completion of three well controlled randomized trials, all of which evaluated a liquid proprietary oral formulation of CBD. Table 2 Adverse events most commonly reported in the randomized double-bind placebo-controlled trial of CBD in comparison with placebo in patients with Dravet syndrome Double-blind trials in Lennox-Gastaut syndrome Two well controlled double-blind trials in patients with Lennox-Gastaut syndrome have been completed, but results to date have only been reported in summary form.
Conclusions and future perspectives The interest in cannabis preparations in the treatment of epilepsies, particularly drug refractory childhood epilepsies, has skyrocketed in recent years. Marijuana and the Cannabinoids. Friedman D, Sirven JI.
Historical perspective on the medical use of cannabis for epilepsy: Phytochemical and genetic analyses of ancient cannabis from Central Asia. On the preparations of the Indian hemp, or Gunjah: Cannabis indica their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases.
Epilepsy and other chronic convulsive disorders. ElSohly M, Gul W. Constituents of cannabis sativa. Oxford University Press; The pharmacological basis of cannabis therapy for epilepsy. J Pharmacol Exp Ther. Marijuana, endocannabinoids, and epilepsy: Mechoulam R, Parker LA. The endocannabinoid system and the brain. Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.
Cannabinoids as hippocampal network administrators. Cannabis and endocannabinoid signaling in epilepsy. Weeding out bad waves: Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy. Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus.
Dynamic changes of CB1-receptor expression in hippocampi of epileptic mice and humans. In vivo activation of endocannabinoid system in temporal lobe epilepsy with hippocampal sclerosis. Medical marijuana in neurology. Detyniecki K, Hirsch L. Marijuana use in epilepsy: Curr Neurol Neurosci Rep. Friedman D, Devinsky O. Cannabinoids in the treatment of epilepsy.
N Engl J Med. Molecular targets for cannabidiol and its synthetic analogues: Inhibition of an equilibrative nucleoside transporter by cannabidiol: Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Voltage-gated sodium NaV channel blockade by plant cannabinoids does not confer anticonvulsant effects per se.
Molecular targets of cannabidiol in neurological disorders. Gaston TE, Friedman D. Pharmacology of cannabinoids in the treatment of epilepsy. Cannabidiol in medical marijuana: Cannabidiol mellows out resurgent sodium current. Progress report on new antiepileptic drugs: Neurological disorders in medical use of cannabis: Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo.
Karler R, Turkanis SA. The cannabinoids as potential antiepileptics. Consroe P, Wolkin A. Cannabidiol--antiepileptic drug comparisons and interactions in experimentally induced seizures in rats. Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. The influence of cannabidiol and delta 9-tetrahydrocannabinol on cobalt epilepsy in rats.
Protective effects of cannabidiol against seizures and neuronal death in a rat model of mesial temporal lobe epilepsy. An electro-physiological analysis of the anticonvulsant action of cannabidiol on limbic seizures in conscious rats. Phytocannabinoids as novel therapeutic agents in CNS disorders. A critical review of the anti-psychotic effects of cannabidiol: Neural basis of anxiolytic effects of cannabidiol CBD in generalized social anxiety disorder: Walter L, Stella N.
The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Neurological aspects of medical use of cannabidiol.
Cannabidivarin is anticonvulsant in mouse and rat. Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. Molecular pharmacology of phytocannabinoids. Prog Chem Org Nat Prod. Pharmacokinetics and pharmacodynamics of cannabinoids.
The current status of artisanal cannabis for the treatment of epilepsy in the United States. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. Single dose kinetics of cannabidiol in man. Eur J Clin Pharmacol. Identification of cytochrome P enzymes responsible for metabolism of cannabidiol by human liver microsomes.
Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: GW Pharma Ltd; [cited Jul 6]. Cannabidiol CBD in Dravet syndrome: Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P 2C There was also a greater reduction in drop seizures in people taking CBD compared to those on a placebo.
Further open label studies have shown that it may also have an anti-epileptic effect in the epilepsies in general. While some studies have also suggested that THC may have an anti-epileptic effect, animal studies suggest it can also trigger seizures. There is no evidence from randomised controlled clinical trials for products with higher proportions of THC more than 0.
Concerns have also been raised about the effect of THC on the developing brain in children and young people. Evidence suggests that chronic exposure to THC can affect brain development, structure and mental health. There is also no good scientific evidence to support suggestions that the addition of THC in combination with CBD increases the efficacy of cannabis-based medicinal products for children. We welcome the rescheduling of these products from Schedule 1 to Schedule 2 that will enable their investigation in clinical trials.
The BPNA also recommends that where children are already taking other cannabis-based products that contain higher proportions of THC, they should be transitioned on to CBD until strong evidence for these products can be produced through clinical trials. The Government has no plans to legalise the use of cannabis for recreational purposes.
Possession of cannabis is illegal. This includes cannabis for medical use unless it has been prescribed for you. Cannabis-based medicinal products can only be prescribed by a specialist. A GP cannot prescribe the medication but could refer you to a specialist. The specialist will discuss all other treatment options with you first before considering a cannabis-based product.
A prescription for medicinal cannabis would only be given when all other treatment options have been tried or are considered unsuitable, and would only be given if the doctor considers it to be in your best interests.
MHRA is working with individual companies to ensure that CBD-based products that make medicinal claims should be licensed and meet safety, quality and efficacy standards to protect public health. To date, the MHRA has licensed no other cannabis based medicinal products as medicines. Skip to main content. In this section What is epilepsy? Diagnosing epilepsy Epileptic seizures Treatment Medication for epilepsy Ketogenic diet Vagus nerve stimulation therapy Epilepsy surgery Deep brain stimulation Care and treatment: Cannabis oil for epilepsy.
FDA Approves CBD-Based Drug to Treat Seizures
The use of medical cannabis to treat seizures has been in the news a lot Cannabidiol, also known as CBD, is a compound extracted from the. drug on Thursday. For children with a rare form of epilepsy, like Paeyton Reuther, CBD provides relief no conventional drug has ever offered. Clarification of the relative contribution of CBD to improved seizure which mention explicitly cannabis as a treatment for seizures and epilepsy.4 .. Although there could be alternative explanations for this finding, it is.