New FDA documents look back on 50 years of marijuana research while previewing future studies on Terpenes and edibles

Since the federal government classified marijuana as Schedule I controlled substances, the Food and Drug Administration has evaluated applications from researchers who want to develop therapeutic drugs using the plant. The FDA has published two documents that look back at more than 50 years of cannabis-based drug research and offer their perspective on what the future may hold for drug development.

This includes looking at a wider range of marijuana consumption methods, such as edibles, as well as lesser-known components and cannabinoids like terpenes.

In a blog and in an article published in Exploration of Medicine, FDA officials stated that over the last 50 years the agency has evaluated more 800 investigational new drugs (INDs) involving marijuana and cannabis-derived product (CCDPs). In the past 50 years, there have been profound changes to product forms, cultural attitudes and the legal landscape surrounding cannabis. All of these changes are felt by FDA.

Authors said that what began as a trickle in applications after the passage of federal Controlled Substances Act in 1970, has now become a flood in recent years as more states have legalized the drug for adult and medical use. In the past decade, the number of cannabis-related applications has been “nearly equal” to the 40-year period before. Currently, the agency is reviewing more than 150 active INDs that involve cannabis-based drugs or related synthetics.

In response to the changing times, FDA has increased its guidance for cannabis researchers and drugmakers. It published a document in 2016 on the development of botanical drugs, and earlier this year it released a separate document that outlined the considerations surrounding hemp and marijuana.

In an article published in Exploration of Medicine, the authors of the FDA agency wrote that the FDA “continues to support robust scientific studies needed to develop new cannabis-based drugs” and is “committed to supporting the development of new drugs through IND and drug approval procedures.”

FDA stated that INDs typically focus on four main clinical areas. Most of them (53%) are centered on addiction and pain medication, while 19% involve neurology, 14% involve immunology and inflammation, and 9% involve psychiatry.

Since the evaluation of cannabis-based medicines began, product form factors have changed dramatically. FDA stated that in the 1970s INDs mainly revolved around smokable marijuana. As more products are developed, in part due to state-level legalization, the FDA has received more drug application requests for oral products and infused food products such as baked goods and sweets.

The article in the journal states that “the past decade has seen a proliferation in new product types being proposed for human clinical trials, as well as an increased number of applications.” In the 1990s, and again in the 2000s, other oral product types were proposed for clinical trials. However, inhalation through cigarette smoke remained the main [route of administration] studied. In the 2010s, the range of products included in clinical trials expanded dramatically to include oral product types as well as other ROAs. The product types that were proposed included sweets, tinctures, tinctures and oils.

FDA states that the shift in form factor is mostly due to cannabis consumers. The authors write that “the emergence of an interest in studying the various ROAs in clinical trials is probably due to the changes in the cannabis consumers in the United States.” In recent years, the consumption of edibles has increased as consumers are no longer only smoking dried cannabis flowers.

Learn about FDA’s history of reviewing clinical research for cannabis and cannabis-derived products in the latest From Our Perspective: https://t.co/Lg07WoD0gB pic.twitter.com/r3oyfKbKKE

FDA Drug Information (@FDA_Drug_Info November 1, 2020

Despite the changes, FDA authors stated that there are still challenges in developing cannabis-related drug for clinical trials. This is especially true when it comes to safety and unknown properties of lesser-known chemical compounds.

The article in the journal states that “These challenges include, but not limited to, the absence and/or insufficient quality and manufacturing information; unknown safety profiles, and unknown benefits/risks of emerging compounds (e.g. hexahydrocannabinol, THC-O); and the complex matrix effect on testing final product formulations.”

The authors do note, however, that the expansion of the form factors studied “correlates” with drug approvals, such as Syndros (2016) or Epidiolex (2018), which are both oral forms. This expansion is also in line with the increase of products available on the state level market, as well as the passage of the Agricultural Improvement Act, i.e. the Farm Bill, on December 20, 2018″.

In FDA’s blog, the authors state that they “expect a new interest in clinical research for CCDPs.”

They also expect to see “the use” of cannabinoids that are less commonly known or newly identified, as well other components in the cannabis plant such as terpenes.

The post states that FDA acknowledges the uniqueness and scientific basis of CCDPs, and the agency will continue to support research on the therapeutic uses of CCDPs. It also says the FDA “will work with companies to bring safe, effective and quality drugs to the market through our drug approval and development process.”

Research into cannabis is difficult due to its Schedule I classification and laws that specifically limit study of marijuana.

Nora Volkow of the National Institute on Drug Abuse has stated that marijuana’s Schedule I status hinders research into the drug because additional registrations and administrative requirements are required. such as the National Center for Complementary and Integrative Health have also blamed federal prohibition for hindering cannabis research.

The changes are happening, but slowly. The DEA ended a long-standing monopoly in marijuana production for domestic research last year. The agency also noted that it is implementing rules for scientists to simplify cannabis access following the passage of a cannabis-research bill in late 2017.

The DEA is currently reviewing the marijuana’s CSA schedule status, after receiving a request from HHS to change marijuana from Schedule I to Schedule III .

DEA’s Schedule 1 drug production quotas are cited as proof that it supports rigorous research on the substances. However, advocates and scientists have criticized its actions as being antithetical to promoting study.

Recently, the agency backed down on , a proposed prohibition on psychedelic substances which scientists claim have value for research.

may be approved by the FDA in the coming year.

Two Republican Senators presented a draft bill in September that they claimed would prohibit the FDA from federally approving marijuana without congressional approval.

The FDA has approved some cannabis-derived medicines and other similar synthetics. However, the agency does not generally approve holistic or plant based medications. HHS proposed rescheduling marijuana after a scientific review directed by President Joe Biden. It would still be federally illegal, except for medical uses with a prescription.

In September, a leading Democrat reintroduced a federal bill to legalize, tax, and regulate marijuana. The bill also included provisions to expunge previous cannabis convictions.

FDA said it conducted a comprehensive review before reaching the conclusion, in January, that a href=”https://www.marijuanamoment.net/fda-announces-it-will-not-issue-rules-to-allow-cbd-as-dietary-supplements-or-food-items-punting-to-congress-for-regulations/” rel=”noopener” target=”_blank>it FDA stated that it conducted a thorough review before concluding in January that could not effectively regulate the market.

It is generally believed that the uncertainty created by this has led to the recent economic struggles of ‘s hemp industry. The uncertainty has also caused confusion in the market as companies continue to sell cannabis products, such as delta-8-THC, which is intoxicating.

In response to this inaction, bipartisan members of Congress have proposed legislation to close the regulatory gap. This will allow for the legal marketing of CBD products as food or dietary supplements. In response to the ongoing inaction, bipartisan congressional lawmakers have a href=”https://www.marijuanamoment.net/new-bipartisan-congressional bills-would allow hemp derivatives like CBD as dietary supplements and food additives/” rel=”noopener” target=”_blank”>introduced legislation to fill the regulatory gap/a> and provide for the lawful marketing of CBD as food items or dietary supplements.

The House and Senate committees requested information from state marijuana regulators as well as hemp industry association. While there were some differences about FDA’s current authority, the majority agreed that Congress should take a holistic approach to this issue, and consider regulations for all hemp-derived cannabis cannabinoids including delta-8 THC.

James Comer, the chairman of the House Oversight Committee (R-KY), announced in April that his committee would launch an investigation into FDA’s CBD review. He asked the agency to turn over any documents that were related to the decision to not regulate the cannabinoid. The congressman had expressed his intention to deal with the lack of rules even before the agency took that decision.

The agency received some praise from both parties earlier this year when it released the first ever guidance on developing psychedelic drugs .