FDA Reviewing the Classification of Marijuana as a Schedule 1 Substance

The US Food and Drug Administration (FDA) is currently conducting research to determine if marijuana should continue to be classified as a Schedule 1 drug in the US, or if its classification should be downgraded, a step toward decriminalizing the drug at the federal level.

The agency is conducting the research at the Drug Enforcement Administration’s (DEA) request, according to a statement from Douglas Throckmorton, Deputy Director for Regulatory Programs at the FDA, at a congressional hearing. The study could lead to the removal of marijuana from the Schedule 1 category of the Controlled Substances Act.

Marijuana’s potential use for a range of medical conditions has gained significant interest over the last few decades. Recently, several states have passed laws that remove state restrictions on health care professionals using marijuana as a medical treatment for a variety of conditions.

Currently, 23 states and the District of Columbia have legalized use of marijuana for medical purposes. Additionally, several other states are considering similar legislation, regarding the use of medical marijuana. Although nearly half of the US states have legalized some form of marijuana, the drug is still classified as a Schedule 1 substance. Drugs that are classified as Schedule 1 drugs have the most restrictions and are considered substances with no medical benefit that are highly addictive.

The reclassification of marijuana could have a significant impact on the cannabis industry, and could help reconcile some of the differences between federal laws and less restrictive state laws.

The agency will make a recommendation after conducting an eight-factor analysis that evaluates marijuana’s abuse potential, its pharmacological effect and risk to public health, among other factors, according to Throckmorton. The FDA must first consult with the National Institute on Drug Abuse and send its recommendation through the Department of Health and Human Services before going to the DEA.

Last updated: 6/24/14; 2:40pm EST


genetic variants

Study Finds Marijuana Use and Schizophrenia May not Have Causal Relationship, but Common Genes

People who are genetically predisposed to developing schizophrenia are more likely to smoke marijuana, according to researchers from the Institute of Psychiatry at King’s College London.

Previous studies have linked schizophrenia and cannabis, however results from the new study suggest the association may be due to common genes and might not be a causal relationship where use of cannabis leads to an increased risk of developing schizophrenia.

The results of the study were published in Molecular Psychiatry. The study is a collaboration between King’s and Queensland Institute of Medical Research in Australia, partly funded by the UK Medical Research Council (MRC).

“Studies have consistently shown a link between cannabis use and schizophrenia. We wanted to explore whether this is because of a direct cause and effect, or whether there may be shared genes which predispose individuals to both cannabis use and schizophrenia,” said Mr. Robert Power, lead author from the MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre at the Institute of Psychiatry at King’s.

Researchers found that schizophrenia may play a role in an individual’s likelihood of smoking marijuana, by showing that the genetic variants predicting schizophrenia can also be used to predict a person’s tendency to smoke marijuana, regardless of their mental health history. The new study included 2,082 healthy individuals, of whom 1,011 had used cannabis. Researchers measured the individual’s genetic risk profile, the number of genes related to schizophrenia each individual carried. The researchers found that those who were genetically pre-disposed to schizophrenia were more likely to use cannabis, and use it in larger quantities than those who do not possess schizophrenia risk genes.

“We know that cannabis increases the risk of schizophrenia. Our study certainly does not rule this out, but it suggests that there is likely to be an association in the other direction as well – that a pre-disposition to schizophrenia also increases your likelihood of cannabis use,” Power said. “Our study highlights the complex interactions between genes and environments when we talk about cannabis as a risk factor for schizophrenia. Certain environmental risks, such as cannabis use, may be more likely given an individual’s innate behavior and personality, itself influenced by their genetic make-up. This is an important finding to consider when calculating the economic and health impact of cannabis.”

Schizophrenia is a common and severe psychiatric disorder, which affects roughly one in 100 people. Typically, the disorder begins in late adolescence or early adulthood. Most common symptoms of schizophrenia include disruptions in thinking, language and perception and often includes psychotic experiences such as hearing voices or delusions.

Source: Power, R. et al. ‘Genetic predisposition to schizophrenia associated with increased use of cannabis’ published in Molecular Psychiatry.

Last updated: 6/24/14; 12:10pm EST




Marijuana Research

30 Members of Congress Ask HHS to Facilitate Medical Marijuana Research

On Tuesday, thirty members of Congress sent a letter to the Secretary of the Department of Health and Human Services (HHS), requesting that the government to ease the process of obtaining marijuana for research purposes.

The letter, led by Reps. Earl Blumenauer, H. Morgan Griffith, Dana Rohrabacher and Jan Schakowsky, was sent to HHS Secretary Sylvia Matthews Burwell, in support for increasing scientific research on the therapeutic risks and benefits of marijuana.

The letter comes shortly after the House voted to block the Drug Enforcement Administration (DEA) from interfering with medical marijuana operations that are legal under state laws. Additionally, just last week, physicians claimed that the agency had threatened to revoke their license because of their involvement in medical marijuana operations.

The letter asks the Burwell “take measures to ensure that any non-National Institutes of Health (NIH) funded researcher who has acquired necessary Food and Drug Administration (FDA), Institutional Review Board (IRB), Drug Enforcement Administration (DEA) and appropriate state and local authority approval be able to access marijuana for research at-cost without further review.”

Currently, 22 states and the District of Columbia have passed laws that legalize the use of medical marijuana. Even though almost half of the states in the US have legalized some form of medical marijuana, the federal government still labels marijuana as a Schedule I substance. Unlike any other drug classified as a Schedule I substance, marijuana requires an additional Public Health Service review for non NIH-funded protocols. Under the review process, the University of Mississippi contracted by the National Institute on Drug Abuse (NIDA) is the only source of marijuana that can be legally used for research.

“In light of the fact that substances like opioids and barbiturates have been researched and developed for human use, it would seem that we should investigate the legitimate medical uses of marijuana. We request that you review and revise the HHS Guidance to eliminate what we believe to be an unnecessary additional review process. NIDA should provide marijuana at-cost to all non-NIH funded marijuana research protocols that have successfully obtained necessary FDA, DEA, IRB and appropriate state and local authority approval,” the members of Congress write.

There is significant anecdotal evidence from patients, caregivers and physicians of marijuana’s therapeutic benefit for treatment of individuals suffering from cancer, epilepsy, glaucoma, anxiety, chronic pain and more. According to the letter, over one million Americans currently use marijuana for medicinal purposes at the recommendation of their doctor. Unfortunately, scientific research demonstrating these benefits has often been hampered by federal barriers. In the letter, the members of Congress say that more scientific information on the therapeutic risks and benefits of marijuana is needed.



Governor Cuomo Pushes for a Stricter Medical Marijuana Bill

Today, New York Governor Andrew Cuomo said that he would not sign a bill that would legalize medical marijuana in the state unless several changes were implemented.

Cuomo has delivered a list of demands that he requires prior to supporting the medical marijuana bill, known as the Compassionate Care Act. Negotiations between Cuomo’s office, the Assembly and the Senate began only late last Thursday and are due before midnight so the Legislature can vote on the bill before the session concludes June 19.

Cuomo’s full list of changes was obtained by advocates, many of which are already addressed in the current legislation. The delay in announcing these demands have caused many to believe that he is not serious in passing it. Sponsors of the bill have already agreed to several of the changes to appease Cuomo; however additional changes require restricting eligible diseases, banning smoking, and lowering doses.

Cuomo’s demands include eliminating serious conditions, including Alzheimer’s, ALS, and muscular dystrophy, and preventing cancer patients and individuals living with HIV from using medical marijuana to treat the side effects of their medications and chemotherapy, like nausea, wasting, and treatment-related pain. Additionally, Cuomo wants to eliminate post traumatic stress disorder (PTSD) and traumatic brain injury, conditions for which medical marijuana has shown to be beneficial. Cuomo requests the removal of a health advisory panel that would decide which disease the drug could be used for and instead giving that authority to New York’s health commissioner.

The changes also include reducing the amount a patient could receive per month from 2.5 ounces every 30 days to 2 ounces.

Cuomo’s changes would also require physicians recommending medical marijuana to be pre-approved by the Department of Health (DOH) and give DOH the ability to over-ride the recommendations of physicians participating in the program in regards to the dosing and administration route. He also recommended reducing the number of manufacturers in the state to five and the number of dispensaries to twenty for the entire state.

“Governor Cuomo is proposing unprecedented interference in the doctor-patient relationship and erecting so many barriers to participation in the medical marijuana program that few, if any, physicians will take part. There is no other medication for which DOH is allowed to come in and abridge the authority and particulars of a physician’s recommendation to his or her patient. I am hoping that such overly restrictive and intrusive language does not appear in the final negotiated bill,” said Sunil Aggarwal, MD, PhD, Co-chair of NY Physicians for Compassionate Care, a group representing more than 600 New York physicians.


GW Pharmaceuticals Provides an Update for its Cannabinoid Pipeline

GW Pharmaceuticals recently provided an update on its cannabinoid pipeline and its progress in the treatment of epilepsy, diabetes and schizophrenia.

The company has completed a Phase I clinical trial of GWP42006 (CBDV), a product which features the non-psychoactive cannabinoid cannabidivarin (CBDV) extracted from the cannabis plant, for treatment of epilepsy. The Phase I single ascending and multiple dose pharmacokinetic and safety study included 66 healthy subjects, and demonstrated no safety or toxicity signals. CBDV was well tolerated, even at the highest tested dose, and no significant adverse effects were observed.

In pre-clinical models of epilepsy, CBVD has shown the ability to treat seizures with significantly fewer side effects than anti-epileptic drugs currently approved. The drug appears to use a different mechanism of action to currently available treatments. The company said that it plans to commence a Phase II study evaluating the drug, using doses identified in the Phase I study, in patients with epilepsy later this year.

GW has been granted a patent for the use of CBDV in the treatment of epilepsy by the Intellectual Property Office in the UK. The patent covers the use of the drug alone or in combination with standard anti-epileptic drugs or in combination with other cannabinoids, providing the company exclusivity until March 30, 2030. Currently, the same patent is in prosecution with the United States Patent and Trademark Office.

Additionally, Epidiolex, GW’s other epilepsy candidate, has received orphan drug designation from the US Food and Drug Administration (FDA) for the treatment of Dravet syndrome and Lennox-Gastaut syndrome, two infantile onset drug-resistant epilepsy syndromes. Epidiolex contains a plant-derived cannabidiol (CBD) as its active ingredient and is one of the important drugs that GW has been associated with.

The company also provided an update for its GWP42004, which is currently in a Phase II study for treatment of patients with type 2 diabetes. The orally administered product features plant-derived tetrahydrocannabivarin (THCV) as its active ingredient. THCV is distinct from THC, and does not share its intoxicating psychoactive effects.

The 12-week randomized, double blind, placebo controlled study’s primary objective is to compare the change in glycemic control in patients with type 2 diabetes when treated with one of three doses of GWP42004 or placebo as add-on therapy to metformin with the primary endpoint being change from baseline to the end of treatment in mean glycosylated haemoglobin A1c (HbA1c). Additionally, the study will evaluate the safety and tolerability of the drug, and is expected to enroll 200 patients. According to GW, the study is estimated to be completed by the second half of 2015.

GW has also commenced a Phase IIa trial, evaluating its GWP42003 for treatment of patients with schizophrenia. The primary objective of the study is to compare the change in symptom severity in patients with schizophrenia or related psychotic disorder when treated with GWP42003 or placebo, added to first-line anti-psychotic therapy over a period of six weeks as change from the baseline to the end of treatment using the PANSS2 total score. Additionally, the study will evaluate the effect of the drug on quality of life and cognition and will assess the safety and tolerability of GWP42003, a drug with featured purified CBD as its active ingredient. Approximately 80 patients are expected for enrollment, with an estimated completion date of the second half of 2015.

“While much of the recent attention regarding GW has been associated with our childhood epilepsy and cancer pain development programs, we continue to make great progress with our pipeline programs, further demonstrating the breadth of our proprietary cannabinoid product development platform to yield interesting and therapeutically beneficial product candidates,” said. Dr. Stephen Wright, Director of Research and Development, GW Pharmaceutical. “As GW continues to progress its clinical work with cannabinoids, our pipeline has the potential to yield, as it did with Epidiolex, a flow of exciting new product candidates in a wide variety of therapeutic areas.”

GW said its Sativex is in Phase III development for cancer pain, as well as multiple sclerosis spasticity. Additionally, GP42003 extract is in Phase II clinical development for ulcerative colitis and its GWP42002:GWP42003 is in Phase Ib/IIa clinical development for recurrent glioblastoma multiforme.

Source: GW Pharmaceuticals plc

Last updated: 3/18/14; 11:50am EST