PTTC NCO - Webinar - CBD - Potential Harms, Side Effects, and Unknowns
(August 8, 2023)

Here are some observations from the Tuesday August 8th Prevention Technology Transfer Center Network Coordinating Office (PTTC NCO) webinar titled “Cannabidiol (CBD): Potential Harms, Side Effects, and Unknowns.”

My top 5 takeaways:

• PTTC NCO—established to further prevention efforts of the federal Substance Abuse and Mental Health Services Administration (SAMHSA)—featured programs intended to reduce cannabis and cannabidiol (CBD) use.
  • At time of publication, the Prevention Technology Transfer Center (PTTC) Network included 12 Domestic Regional Centers, 2 National Focus Area Centers, and the Network Coordinating Office, whose staff assisted prevention training and substance use disorder (SUD) services nationwide.
    • The Northwest PTTC hosted a December 2020 webinar on “The More the Merrier? THC Potency in the Legalization Era.”
  • Project Coordinator Van Wilson welcomed attendees and described PTTC as a SAMHSA “training and technical assistance grantee that exists to serve the substance use prevention workforce.” He shared that there were “at almost a thousand people here” to learn about a SAMHSA February 14th advisory on CBD (audio - 2m, Video - PTTC NCO, transcript).
  • Wilson described how he worked the PTTC NCO cannabis prevention working group Chair Britany Wiele, Pacific Southwest PTTC Training and Technical Assistance Specialist, and Co-Chair Scott Gagnon, New England PTTC Associate Executive Director. Wilson then said work groups were based on the idea of “six subject matter areas of expertise” (audio - 2m, Video - PTTC NCO).
    • Community coalitions and collaborators
    • Building Health Equity & Social Justice
    • Data-informed decisions
    • Implementation Science
    • Cannabis Prevention
    • Workforce Development
  • Wiele mentioned that the work group “existed to develop training and technical assistance tools, products and service related specifically to cannabis prevention education.” She highlighted that they collaborated with the SAMHSA Evidence Based Resource Center “on this event to promote the organization’s latest advisory, ‘CBD - Potential harms, Side effects, and Unknowns’” (audio - 1m, Video - PTTC NCO).

• SAMHSA staff and a health researcher introduced the topic of CBD products and potential risks for consumers before going into some background on the compound and hemp.
  • Wiele welcomed the presentation speakers:
    • Humberto Carvalho, SAMHSA Project Officer and National Mental Health and Substance Use Policy Laboratory Public Health Advisor
    • Krishnan Radhakrishnan, SAMHSA National Mental Health and Substance Use Policy Laboratory Senior Advisor
    • Amy Berninger, Abt Associates Health Research, Monitoring, and Evaluation Senior Associate
  • Carvalho remarked that the advisory he would speak on was “all about CBD, and the risks associated with using commercial grade over-the-counter CBD.” He expected the presenters to begin with “crash course[s]” in chemistry, biology, and legislating in order to explain how the cannabinoid had become available, “followed by who uses it, a little bit of prevalence rates, and demographics [and] we examine why we should be concerned about CBD usage, especially among children and women of childbearing age” (audio - 3m, Video - PTTC NCO, presentation).
  • Radhakrishnan kicked off his comments by “introducing” the cannabis plant, which he said was “a genus of flowering plants in the hemp family cannabaceae, which includes hops,” along with “so-called cannabinoids” (audio - 7m, Video - PTTC NCO).
    • He told attendees cannabinoids could be found “in the shiny white dots which coat the leaves, the stems, and branches and this whole thing is harvested, dried and cured and sold as hemp buds. People also buy…dried hemp leaves which they either smoke or make into tea.”
    • Among the cannabinoids found in the plant, Radhakrishnan noted delta-9-tetrahydrocannabinol (delta-9-THC) and CBD were “two of the most abundant.” In talking about the chemistry of CBD, he reported that the “structure of this molecule was worked out in 1963, but it wasn't much interest because it didn't have any intoxicating effects.” When the structure of THC was determined in 1964, “its effects were elucidated by simply giving the stuff to volunteers and seeing what happens.” But “it was not until the mid-to-late 1980s that somebody discovered a membrane-bound specialized protein called receptor…made up of lipids, phospholipids, proteins, cholesterol” which can “allow stuff to go into the cell and leave the cell,” Radhakrishnan remarked. “Several…proteins of this act as something called…receptors, which this particular receptor binds THC,” which he said made the compound a “signaling molecule” for a “cascade of chemical reactions called the signaling cascade” which our bodies interpreted as “getting high.”
    • Radhakrishnan noted the different types of receptors for cannabinoids, and mentioned researchers were interested in figuring out why the body had cannabinoid receptors since “all this takes energy in the body [which] usually doesn't waste energy making things.” He said there was evidence that the body produced its own endogenous cannabinoids—called endocannabinoids—as part of an “entire system called the endocannabinoid system, or simply ECS.” Radhakrishnan talked about the study of the ECS, and “although the precise mechanism is still not clear it is agreed that the ECS is important in human reproduction,” so “exogenous cannabinoids” such as CBD or THC “may interfere with it” adversely.
    • Delta-8-THC and delta-10-THC, were “chemical cousins” of delta-9-THC,  “usually synthesized from hemp,” commented Radhakrishnan, and “new” cannabinoids were “entering the market all the time.” While there were similarities in the chemical structures of cannabinoids, they elicited differing effects, and he stressed that CBD wouldn’t “give a high,” with delta-8 and delta-10-THCs proving to be less intoxicating signaling than delta-9-THC.
  • Turning to hemp, Radhakrishnan stated cannabis was the “same plant” as hemp yet was distinguished in US law, and legalized in the 2018 Agricultural Improvement Act (commonly referred to as the US Farm Bill), establishing hemp plants as those with “with a delta-9-THC concentration that's no more than 0.3% on a dry weight basis.” The 2018 law also defined “marijuana as a cannabis plant that simply has more delta-9-THC than 0.3%,” he added. Radhakrishnan expanded on how different receptors were more common in different parts of the body. The “method of action” for CBD was still being studied, he said, “but it's known to inhibit the breakdown of the natural endocannabinoids that I mentioned, and possibly THC.” According to Radhakrishnan, “if you can’t get rid of it, then obviously it's going to hang around. So, using CBD with THC may exacerbate the effects of THC on the body simply because it's hanging around for much longer periods of time” (audio - 3m, Video - PTTC NCO).
    • Hemp as a crop distinct from prohibited cannabis became prominent during World War II in the Hemp for Victory campaign.
    • Some research has suggested that CBD slows the metabolism of THC when ingested orally in edibles, though other studies found CBD content may limit psychoactive effects of THC when taken intravenously..

• Presenters spoke about the retail market for hemp consumables with CBD and consumer trends associated with their use (audio - 4m, Video - PTTC NCO).
  • Radhakrishnan commented that the 2018 Farm Bill had legalized hemp plants and "effectively permitted" a commercial market for "hemp-derived cannabinoid products,” a “loosening of restrictions on CBD [which] opened the floodgates to CBD marketing and sales.” He asserted that these items had been "increasingly marketed as a cure-all for a range of medical conditions and ailments despite limited evidence for their effectiveness.” Radhakrishnan acknowledged that Epidiolex had received federal approval as “pharmaceutical grade CBD which is prescribed for epilepsy,” and approved for persons older than one year by the US Food and Drug Administration (US FDA) with their physician’s prescription. By contrast, CBD products in stores were “not FDA approved,” he emphasized.
  • Claiming to speak to “how does the FDA feel about” retail CBD items, Radhakrishnan referred to a January 26th call from FDA leaders for a new “regulatory pathway” for the products. He reported that CBD product claims hadn’t been proven, and there was no federally approved avenue for CBD in food or dietary supplements. Radhakrishnan said the availability of CBD products “varies by state" but had been stocked in major retail chains, local convenience stores; “you can even buy it in gas stations.” However, he claimed 66% of sales happened online, though he predicted that was decreasing, as there were now CBD “vending machines in several states, and of course, several countries in the world.”
  • Berninger then took over to describe “who is using this stuff anyway,” indicating that the largest consumer segment was adults between 18 and 29, and “nearly half of those adults who use CBD products believe that they are regulated by the government which likely contributes to the large number of individuals who feel comfortable using them.” She said a “significant market” existed, and “according to the Brightfield Group” there was a $4 billion market for CBD in the US “projected to top 25 billion by 2025.” Product types were often “oils or gummies,” but a variety of items were being sold, including teas, creams, lotions, cosmetics, smokable products, or those introduced “into specific areas of the body in the forms of eye drops and suppositories,” she added, emphasizing that there were “even CBD products for pets now" (audio - 2m, Video - PTTC NCO).

• Next, presenters covered risks related to CBD and THC items, including some which were said to be the result of the absence of regulation of the substances by federal authorities (audio - 7m, Video - PTTC NCO).
  • Berninger claimed that use of CBD products “can cause common side effects and adverse reactions” which were experienced “by 10% or more of users.” Specifically: “drowsiness and/or fatigue, decreased appetite, diarrhea, increased liver enzymes, rash, insomnia; and other sleep disorders and infections,” which she said were similar “to some [adverse reactions] associated with other anti-epileptic drugs.” Additionally, “CBD may also produce psychotic effects or cognitive impairment in individuals who regularly use delta-9-THC products, like marijuana,” Berninger warned.
  • Turning to several factors that could impact the likelihood or severity of adverse reactions, Berninger named “the strength and purity of the product, the amount used, the mode of administration, concurrent substance use and misuse such as the legal and illegal drugs and alcohol, and interactions with prescribed drugs or other medications.”
  • Berninger brought up some problems made worse due to a lack of national standardization and oversight of CBD products:
    • Inaccurate labeling of products: “one study found that among 84 CBD extracts purchased online from 31 companies the CBD concentration was only labeled accurately in 31% of products. Almost 43% of products were under labeled, and 26% were over labeled.”
    • Manufacturing wasn’t regulated by any federal agency, so “products may be produced using unsafe manufacturing practices and without adequate process controls in place” leading to products that could “contain biological and chemical contaminants such as pesticides, heavy metals, bacteria, and fungus all of which pose health hazards to those who use them, especially in young children and pets.”
    • THC content: the “previously mentioned study of 84 commercial CBD extracts also found that over 21% of the samples tested contained unlabeled delta-9-THC, and another study found that 12% of hemp oil products available commercially exceeded the 0.3% THC concentration limit.”
    • People consuming CBD could “still screen positive" for cannabis, resulting in “work-related, legal, and health risks.”
  • Berninger reiterated that with no US FDA regulation—except for Epidiolex—CBD items were “not considered safe to use.” She was under the impression that some consumers doubted items could have “intoxicating properties because they are labeled as a hemp product.” Additionally, she called out a particular concern about “unintentional product exposure to children and pets, and potential adverse effects such as vomiting, hallucinations, and loss of consciousness.” Berninger mentioned that “CBD products may be contributing to the increasing number of CBD related emergency room visits.” She acknowledged, “literature on this topic is sparse but growing,” citing a “paper published in clinical toxicology in 2023 [that examined] CBD exposures documented by America's poison centers” which found “an increasing trend in CBD exposure cases managed by poison centers and serious medical outcomes in temporal association with exposures to non-FDA approved CBD products.”
  • There was a "special concern,” said Berninger, when people used products for medical issues “unaware that they may contain impurities and different CBD doses than used in clinical studies” and without consulting a healthcare provider. She argued this was especially troubling for pregnant or breastfeeding women, and for children. “Both delta-9-THC and CBD cross the placenta and can impact the fetus directly,” commented Berninger, as the placenta had cannabinoid receptors and “one study detected CBD in the stool of newborns.” She indicated there was evidence that THC exposure in utero could impact “brain development in the womb and increase[d] the likelihood of stillbirth or premature birth.” Furthermore, “THC can be passed on to an infant through breast milk and experts think this may also be true for CBD,” Berninger told the group.
  • Intentional and unintentional exposure of children to CBD was increasing, she noted, based on “poisoning cases in children after eating edibles or overdosing on” a product belonging “to a parent or caregiver, which may be mistaken for regular candy.” Berninger mentioned that emergency room “visits by children for CBD intoxication [were] also increasing as the use of CBD products increases by adults, especially edibles, unintentional CBD intoxication in children will likely increase as well.”
    • Berninger didn’t expound on the distinction between cannabis ‘intoxication,’ and Radhakrishnan’s prior comment that CBD didn’t cause a ‘high.’
  • Radhakrishnan echoed the increasing availability of CBD products, repeated points by Berninger, and offered some concluding remarks (audio - 4m, Video - PTTC NCO).
    • Epidiolex was a “purified product…in a reliable dosage form, and a reproducible route of delivery” with federal approval to be prescribed, but no other CBD products were considered safe for human consumption, or as “treatment for any physical or mental condition.”
    • US FDA staff wanted a new regulatory framework for CBD.
      • In an agency presentation for webinars in April and May 2023, US FDA staff offered more details on the benefits of a new pathway for hemp oversight, than on how such a pathway would be defined and implemented. However, Patrick Cournoyer, Cannabis Product Committee Lead defined it broadly as a ‘harm-reduction’ framework.
    • “The CBD marketplace [was] largely under regulated, leaving it up to the consumers to do their own research, buyer beware.”
    • “Interest in CBD is increasing across all age groups, and use for pets is also mushrooming,” a trend attributable to “aggressive marketing and false health claims.”
    • Purity concerns in CBD items existed since “biological and chemical contaminants have been found in many samples such as heavy metals, including copper, nickel, lead, pesticides, bacteria, fungus, and mold.”
    • The presence of unlabeled cannabinoid content “may produce unintended intoxication, and potential run-ins with the law.”
    • Health and impairment risks were more pronounced for children, so parents should communicate their concerns to youth and “not allow their children to use over-the-counter CBD" or allow any temporary guardian to enable use. “Pregnant and breastfeeding women should also be advised to avoid CBD products as its effects on developing fetus and child [were] still being evaluated.”
  • Carvalho thanked his colleagues and encouraged people to follow the work of SAMHSA and the PTTC NCO cannabis prevention working group, or reach out via ebprc@samhsa.hhs.gov for more information.

• Staff summed up what they’d learned and opened the floor to questions on commercial CBD production; state laws; interactions with medications or alcohol; and other issues.
  • Wilson thanked the presenters, and turned to questions posted in the chat box. He reshared the US FDA advisory on CBD, and acknowledged other cannabis prevention work group members (audio - 4m, Video - PTTC NCO):
    • Michelle Frye-Spray, PTTC - NW Project Co-Director
    • Ken Winters, PTTC - National American Indian and Alaska Native Advisory Council
    • Susie Villalobos, PTTC - National Hispanic and Latino 
    • Jeanne Pulvermacher, PTTC - Great Lakes State Project Manager - Michigan
    • Deborah Nixon-Hughes, PTTC - Central East Project Director
    • Taylor Cook, PTTC - Mountain Plains Training Coordinator
  • “Can you speak…to the difference between pure CBD and commercial CBD?” (audio - 1m, Video - PTTC NCO)
    • Radhakrishnan said pure CBD would have “nothing else in there…and commercial CBD, God only knows what's in it. It's not regulated. Nobody knows how it's made except the manufacturer. The purity is unclear unless you take it to the laboratory yourself.”
      • In 2023, Washington State lawmakers learned that achieving pure CBD was difficult to legislate, and even the website for Epidiolex hedges that the medicine “is nearly 100% pure CBD.”
  • “What's the reason that there are so few FDA approved CBD products, and is the FDA working towards approving more?” (audio - 1m, Video - PTTC NCO).
    • The US FDA approval process was complex, Radahkrishnan commented, “and you have to invest money.” Research had to demonstrate a product’s effectiveness and safety, “and nobody seems to have stepped up to the plate and done randomized control trials which are expensive and lengthy.” Additionally, that agency didn’t approve supplements, he said, though “if problems are found with it” or CBD was being sold with medical claims being made “then the FDA will step in.” He explained vitamins didn’t require FDA approval as they didn’t claim to treat any medical condition.
  • With attendees expressing “some surprise about CBD being in the same family as hops,” Radahkrishnan noted “biology is biology,” and cannabis was in the same family of plants as hops and mulberries (audio - 1m, Video - PTTC NCO).
  • Someone inquired “about states that…legalized, and…what's in the laws or the regulations around CBD” (audio - 1m, Video - PTTC NCO).
    • Gagnon shared the view that “states don't tend to put a lot of focus on CBD” and focus more on THC, feeling there were "very few states that address THC content in their laws."
    • In Washington state, officials began to note complaints related to the accessibility and safety of hemp-derived cannabidiol products with CBD or cannabinoids synthesized from CBD extracts. The Washington State Liquor and Cannabis Board (WSLCB) successfully lobbied for an agency request bill on cannabinoid regulation, SB 5367, which was signed into law on May 9th. Agency leaders initiated rulemaking to implement the law on June 21st.
  • “A licensed pharmacist in my area creates his own CBD oil for sale. Should this be considered safer than…over the counter CBD oil?” (audio - 1m, Video - PTTC NCO)
    • Radahkrishnan responded that this "depends on your pharmacist, how well do you trust him or her?”
      • WSLCB staff had considered proposing agency request legislation to allow medical cannabis patients to contract directly with licensed producers due to a reported preference some patients had for unlicensed farmers markets, even allowing them to forego testing the plants for pesticides or contaminants.
  • An attendee asked “can [you] please speak to concerns about CBD and medication interactions?” (audio - 1m, Video - PTTC NCO)
    • “There are many, many medications…that interact” with CBD, Radahkrishnan stated, referring to drugs.com materials on CBD where he remembered "almost 600” interactions being listed.
  • “Who is regulating CBD infused alcohol?” (audio - 1m, Video - PTTC NCO)
    • Radahkrishnan didn’t know of any regulatory body overseeing that, though Gagnon speculated that depending on where it was manufactured there could be a state agency with authority over those products. Wilson noted that 2023 legislation passed in Washington state outlawed products with THC and alcohol, though on July 3rd WSLCB staff reported the law was duplicative of existing prohibitions on such products. “So it is emerging,” he added.
  • Bringing the session to a close, Wilson called for attendees to share what they’d learned from the presentation, noting that comments reflected "lots of concerns about contamination,” as well as the “lack of regulation.” Weile highlighted that with several comments about cannabis and pregnancy “we will be having a webinar next month focusing on that.” Wilson encouraged people to sign up for the PTTC monthly newsletter (audio - 4m, Video - PTTC NCO).