NW PTTC - Webinar - Pharmacology of Cannabis
(October 29, 2020)

Thursday October 29, 2020 11:00 AM - 12:30 PM
Prevention Technology Transfer Center (PTTC) Network - Logo

The Northwest Prevention Technology Transfer Center (PTTC - NW), serving the United States Department of Health and Human Services (US HHS) Region 10, is led by the Social Development Research Group (SDRG) at the University of Washington (UW) in partnership with Washington State University (WSU), and the Center for the Application of Substance Abuse Technologies (CASAT) at the University of Nevada, Reno (UNR).

This webinar will explore the pharmacology of cannabis. The presenter will cover how cannabis addiction impacts major brain regions and the acute and chronic symptoms associated with cannabis use. Specific features of cannabis dependence and withdrawal will be discussed specifically symptoms that occur when a person is discontinuing its use. The webinar will use Zoom technology and the format will be interactive with ample time for questions.

https://pttcnetwork.org/...macology-prevention-specialists-pharmacology-cannabis

Observations

Ron Jackson, a University of Washington professor, led a wide-ranging webinar for prevention professionals on the plant cannabis, its uses, effects, and modes of action.

Here are some observations from the Thursday October 29th Northwest Prevention Technology Transfer Center (NW PTTC) webinar on the pharmacology of cannabis.

My top 3 takeaways:

  • Ron Jackson, a professor with the University of Washington (UW) School of Social Work, led the presentation with a general review of drug use, abuse, and addiction. He went on to cover a broad spectrum of issues around drugs generally, the history of cannabis specifically, as well as effects, trends, and issues around cannabis use disorder.
    • Jackson opened with a description of a “Continuum of Use” for substances (audio - 3m, video).
      • On one end were people “who had never used any mind-altering substances in their life,” but Jackson felt a majority of people “experiment” for various reasons. This “normal human behavior” would typically, “but not exclusively” occur during adolescence, Jackson explained.
      • Moving along the continuum, experimentation sometimes led to “regular use” of a substance. Jackson felt this was “non-problematic” regardless of the substance's legal status unless it caused “them or anybody around them any problems.”
      • He commented that the next stage “used to be called abuse” but experts were moving away from that wording as “a) It’s a judgemental term, and b) most importantly, there’s no empirical support for what that term means as a diagnostic category.” Instead, Jackson said, the term “substance misuse” was increasingly utilized to mean a person using a substance “in a way that’s causing harm to themselves or somebody else.”
    • Jackson next discussed “Substance Use Disorder” at the “far end” of the continuum of use, also called addiction (audio - 6m, video).
      • He elaborated that there was “stigma” around the term “addiction” which manifested as “the hurt that people feel from judgments of other folks for doing things...that other people might think of as bad.” This stigma was part of the justification for moving away from “abuse” and “addiction” as clinical terminology, he said. The other part of the change was “to make it a person-first language, this is a person with a substance use disorder” as opposed to “a diagnostic label, subject to discrimination and so forth.”
      • Jackson examined several quotes on addiction including former NIDA Director Alan Leshner’s definition that “addiction is a brain disease shaped by behavioral and social context.” He said that Leshner had lectured throughout America in the 1990s and 2000s about information from the National Institutes of Health (NIH) Decade of the Brain, a research initiative which studied addiction’s impact on brain development. Leshner had attributed the behavior to “changes in the brain that lead to persistent drug use,” Jackson noted.
      • Jackson shared current NIDA Director Nora Volkow’s definition that “addiction is associated with altered cortical activity and decision making that appears to overvalue reward, undervalue risk, and fail to learn from repeated errors.” Volkow found the latter part of the definition applied to typical adolescent brains as well, he said. Volkow had worked with a company to establish “the instrumentation to look inside the brain,” which found the prefrontal cortex dealt with “impulse control, of executive function, decision making in human beings and its one of the last brain structures to mature.” Jackson said that substance use could impact the “reward center” of the brain, with regular use leading to a "downregulation of prefrontal cortex vitality, and thus limited ability" for impulse control. As a result, relapsing was “not just an act of will" but a symptom of a physically altered brain, he commented.
      • Susan Sontag, author of Illness as Metaphor, postulated “any disease that is treated as a mystery and acutely enough feared will be felt to be morally, if not literally, contagious.” Before diseases are understood, Jackson stated, “we fear people who have that disorder” and were prone to using social structures to ostracize or to “lock them up.” He argued that “mysteriousness of the origin” of diseases like addiction “make us fear” those with it.
    • Jackson then went through four “Elements of Addiction” which “differentiates misuse from addiction” (audio - 8m, video).
      • Compulsion & Craving. Consisting of both biological and conditional responses, Jackson referred to an “irresistible urge to use.” “Tolerance” occurred via homeostasis wherein a person's body changed from regular use of a substance and looked to “more potent forms or use more often.” Jackson explained the “corollary” to tolerance was “withdrawal” from ceasing use. This “was different for different types of drugs” but “common properties” across withdrawal were “anxiety and drug craving.” A “longer lasting” craving was a kind of “Pavlov’s dog” response to environmental stimulus as individuals used drugs under a variety of circumstances, “when they’re happy, when they’re sad, when they’re bored, when they’re angry, when they’re anxious, when they can’t sleep.” Moreover, substance use could be promoted by external reasons such as time or location, Jackson indicated. Teaching people how to respond to cravings or structure an environment to minimize use triggers was a key part of substance use disorder treatment, he conveyed.  
      • Loss Of Control Over Use. Jackson said one typical attitude of a person with substance use disorder was a plan to stop after a certain limit, but “for reasons that are not clear, their use actually triggers more hunger.” Jackson called attention to the adage among alcoholics that “one’s too many and 15’s not enough.”
      • Continued Use Despite Adverse Consequences. Jackson said this was a “mysterious” element of addiction for substance users and “people around them” as there could be huge consequences around health, employment, “legal issues, and so on.” 
      • Salience Of Use. Jackson said “salience” was “the relative importance” assigned to substance use “because these substances tend to hijack the brain’s reward path.” He stressed that this was an “emotional relationship with that substance” rather than a physical one. Noting Maslow's Hierarchy of Needs, Jackson said substance use disorder undercut people’s basic needs to maintain their relationship with a drug or behavior.
    • Jackson shared information from the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5), saying “the terminology is a little bit different for alcohol use disorders as opposed to cannabis” but constituted the “general category for substance use disorder.” He remarked that tolerance and withdrawal for substances prescribed by a physician “doesn’t really count” as a symptom of substance use disorder even though it could be a “physical dependence.” Generally, “conditions are seen along a spectrum” Jackson added, giving flexibility around the severity of the substance use (audio - 3m, video).
    • Jackson then talked about Theories on the Etiology of Addiction, or the causes of addiction, while qualifying that his expertise was in “how a person treats an individual who is struggling with substance use disorder” (audio - 6m, video).
      • Drug Based. Some theories postulated something "pernicious" about a drug and its ability to “take you over...and rob you of your spirituality.” Jackson noted “most people...don’t become addicted” to most drugs and many experts believed substance use disorders were “dictated by underlying psychopathology.” Jackson added he felt this “does seem to be true” with both biological and psychological conditions. However, this “only typically explains about half of the variance in addiction risk.” 
      • User Based. Psychologically or biologically driven factors can “make a person more inclined to either like the...drug that they’re taking or it makes them feel less bad,” Jackson suggested.
      • Environment Based. He said these theories could explain “the other 50%” in addiction variances, citing Johann Hari’s book Chasing the Scream and TED Talk “Everything you think you know about addiction is wrong,” which identified “a loss of social connection” as one factor perpetuating addiction. Jackson noted “an uptick” in substance use disorder due to the coronavirus pandemic. However, he said, "I can't tell a person why they have a cannabis use disorder" as it was generally too “complex.”
    • The Brain (audio - 2m, video). Jackson said “cannabinoid receptors” in the limbic system caused some people to experience an “elevation of mood” following use. That region of the brain was also tied to memory leading to “craving situations,” he noted. The prefrontal cortex shared a “neurological link” to the limbic system, but in his experience much substance use disorder was “the attempt by this person to modulate negative emotional or physical states” rather than a “hedonistic pursuit of la-la land.”
    • Variables Determining Drug Effects (audio - 4m, video).
      • Dose. “The effects of drugs are dose related,” Jackson established, and while “there’s no known lethal dose” for cannabis, “the higher the doses, the more the effect.”
      • Route of Administration. “Fastest way to get a drug to your brain is to smoke it,” Jackson stated, and with cannabis this was often done by smoking or vaping. However, cannabis “typically has a shorter action over time” from inhalation than from ingesting it, which was slower to impact someone, “but the effects are going to be more profound.”
      • Set and Setting. He described the set as the “internal conditions of the user” while setting was “what’s going on around them.” Jackson said that “at low doses of cannabis, set and setting are actually as important in determining behavior of that person as the drug itself.” A common expression of this variable was poly-drug use, or when people habitually associated or preferred using a combination of substances, he explained.
      • Biochemical Individuality. “Last, but not least” Jackson said this variable was “a very significant driver of how a person feels in response to drug ingestion.” Although a substance “might act as a stimulant in” the majority of people, “in a small percentage of the population” it could “slow things down for that individual.” For cannabis, Jackson argued that “there’s a lot about biochemical individuality and response to cannabis that we don’t know.” He viewed cannabis and cannabinoid research as “in its infancy,” and “because cannabis has been a schedule one drug...there hasn’t been the scientific inquiry into it.”
    • Drug Classification (audio - 1m, video). Cannabis “is in a separate category by itself,” Jackson noted, as its effects didn’t consistently match depressants, stimulants, or hallucinogens.
    • Looking at modes of ingestion, Jackson said for cannabis the typical choices were smoking cannabis flower, vaping concentrates, or infused edibles (audio - <1m, video).
    • History of Cannabis Policy in the U.S. (audio - 4m, video). Jackson reviewed some key dates for policy in the United States, calling cannabis a “demonized” plant.
      • “Cannabis regulation was not a part of the Harrison Narcotic [Tax] Act back in 1914,” but came under federal control through the Marihuana Tax Act of 1937, Jackson said. At that time, Harry Anslinger, head of the Federal Bureau of Narcotics, worked to demonize the drug in part by funding “propaganda” like the 1936 film Reefer Madness, he told the group. Jackson said that as politicians “tend to fear taking progressive social action...nothing really ever happened about legalization of marijuana.” Furthermore, “it's hard to study the social control...of substances in our country without encountering racism" as many prohibition policies were “often racist in their intent" since the government “couldn't necessarily legislate against” racial groups but could target “a substance that they might be using.”
      • In 1970, cannabis received the highest drug scheduling possible under the Controlled Substances Act, Jackson noted, keeping the plant from being “bought, sold, produced, trafficked, researched, anything” which "suppressed scientific inquiry" about both "good things as well as the not so good things about marijuana.” 
      • The prohibition of cannabis began to be dismantled in 1996, he said, with California’s approval of the first medical marijuana law by way of Proposition 215.
    • Recent Trends In Use (audio - 5m, video). Jackson reported that the largest single increase in cannabis use since legalization was among the “55 to 64 year old group.” With changes in cannabis laws enacted or proposed across the country, he viewed the primary driver for reform was tax revenue for states. For Washington, Jackson pointed to data for fiscal year 2020 showing $1.27 billion in legal cannabis sales generated $486 million in revenue, of which 73% went towards the state’s general fund and the rest went to “cannabis treatment, prevention, and research.” Though rescinded in 2018, the former Cole Memorandum had provided federal guidance to enable state legalization, including “keeping cannabis out of the hands...of adolescents” and that state-legal cannabis industries weren't “supporting organized crime.”
    • Cannabis Evolution (audio - 1m, video). For cannabinoid concentration, Jackson suggested that tetrahydrocannabinol (THC) was the “predominant psychoactive substance” in the drug, and flower cannabinoid concentration had increased since the 1980s. There was also a “significant dose difference” for cannabis concentrates, he added. 
    • Cannabis Cultivars (audio - 1m, video). Jackson talked about a friend who claimed society would see "400 pound tomatoes" if cannabis hybridization techniques were applied to them. While some cannabis effects had been categorized by cultivar, Jackson found the user remained the primary factor in determining effects.
    • Cannabinoids and Terpenes (audio - 3m, video). Jackson reported that "the higher the content of THC in a plant, the less therapeutic it seems to be" with higher THC content seeming to “negate some of the healing properties” of the plant. Jackson spoke to the legal distinction of hemp “required by law” to have “no more than 0.3% THC content” and noted many farmers cultivated hemp to add cannabidiol (CBD) to other products for the compound’s “analgesic properties and anti-convulsive properties.” For terpenes, he said research was ongoing “about the degree to which those terpenes also have a psychoactive effect as well,” adding that they could be “responsible for the couch-lock that you might feel.”
    • Endocannabinoid System (audio - 3m, video). Jackson laid out the fundamentals of this bodily system, stating “we manufacture our own cannabinoids” and had two types of receptors for them throughout our bodies. “CB1 types” were concentrated in the brain “and in the spinal column, sort of, in the nervous system,” he said, while CB2 receptors were less abundant in the body and “involved in modulating immune response.” The common endocannabinoids in the body were anandamide and 2-arachidonoylglycerol, both fairly short lasting and potentially responsible for the “runner’s high” felt after exercise. Jackson said doctors previously attributed this sensation to endorphins, but “it’s probably not, it’s probably more of an endocannabinoid-related phenomenon.” In a 2013 study of the endocannabinoid system, researchers “talk about the entourage effect, that it’s not just CBD, it’s not just THC, it’s not just cannabinol (CBN)” but that all of them were “important in delivering the beneficial effects, the medicinal effects of cannabinoids.” Jackson showed a breakdown of cannabinoid receptors in the brain, saying most were CB1 receptors and “receptor sites for the THC, that’s why you get the brain kind of effects that you get” from consuming cannabis.
    • Acute Effects (audio - 5m, video). Jackson said acute effects “depends on what dose you’re taking, kind of depends on what the strain is, depends on how you’re getting it in your body” as well as tolerance and previously mentioned conditions like set or setting. Overall, he pointed to, “mild” cardiovascular effects and bronchodilation effects which could account for some of cannabis’ medical potential. “We don’t know much about the effect on the neurohormones, the endocrine system” or cannabinoids impact on the immune system which would still be impacted “by diet and exercise,” Jackson indicated. He then mentioned effects on the mind and behavior from cannabis, and claimed those using the drug “like the feeling that they get” and gravitate between “relaxed, disinhibited, more social, or they feel kind of interior, and kind of locked in, and maybe suspicious.” Regular cannabis users’ responses could also change over time, going from relaxation to “panic reactions,” Jackson warned. THC impaired perception of time and reactions, he commented, “that’s why people are impaired from a driving standpoint.” This was the impetus, Jackson believed, for I-502 including a per se standard for impaired driving, set at five nanograms per milliliter, though he observed that “there’s not a huge amount of empirical support for that number” as some people demonstrated “physiological tolerance and behavioral tolerance” with the latter meaning the person “learned to do things under the influence.” He said this type of tolerance meant people “can perform psychomotor tasks perfectly fine” with larger concentrations of THC above the State’s limit, but “that’s where the line is in our place.”
    • Chronic Use Consequences (audio - 4m, video). Jackson stated that “use on a regular basis” left THC in the body “so you don’t have to be a daily user to develop tolerance,” but that use “once every couple of weeks or once a month, that’s not sufficient to get the tolerance.”
      • Smoking anything “does damage to your respiratory system,” he said, calling attention to illnesses beginning around 2019 attributed to “adulterants” in unregulated vaping products.
      • Cannabinoid Hyperemesis Syndrome, Jackson reported, was “a fancy word for throwing up a lot” following “higher dose use” of cannabis over a longer term.
      • Jackson said there was also evidence of immune system suppression for the body’s T cells “but we don’t know” to what extent modifying cannabinoid concentrations might impact this. 
      • “Cognitive Impairment also occurs,” he remarked, though there wasn’t a good understanding of “the degree to which that happen[s].” Jackson said his clinic participated in a “randomized controlled trial” studying people who reported concern over their cannabis use. Within this trial a “sub-study” emerged to look at cognitive impairments, he explained, finding evidence in those consuming “a lot of high doses for a substantial period of time” and not in “lighter users.” Jackson added that an extended study of children eight to 10 years old was underway to “understand who is more vulnerable and what happens, not just with cannabis, but all psychoactive drugs” and look for “brain changes, behavioral changes” to help experts understand impacts of regular use.
    • Cannabis Use & Psychosis (audio - 1m, video). Jackson described several “association studies, they’re not causation studies” linking cannabis to an increased risk of psychotic episodes. He said, “There’s no animal model to study the onset, the generation of schizophrenic-like symptoms in animals” in a way to “correlate that to human beings.” He said “a kid who has a family history of mental illness” appeared to possess “a greater risk for developing psychosis as a result of their use of cannabis.”
    • Adolescent Use (audio - 2m, video). Jackson had “no problem at all with the legalization of cannabis use by adults,” but held “a lot of concerns about...cannabis use by adolescents" primarily due to the drug’s impact on “a brain system that’s not yet mature.” Early adolescent use was a “significant predictor” of future substance use disorder, he said, citing a New Zealand longitudinal study of adolescent drug use as part of the reason he tells his “teenage grandkids ‘Don’t do that.’”
    • Problems Associated With Marijuana (audio - 1m, video). Looking at problems from regular use, Jackson said he’d omitted the “most endorsed reason” participants in his clinical study offered for changing their cannabis habits: “they were worried about drug screen urinalysis” and being “able to pass a workplace urine test, or a pre-employment work test,” since THC stayed in the a person's system for several weeks.
    • Cannabis Withdrawal Symptoms (audio - 1m, video). Jackson stated that this was a condition identified recently, and that THC already in the body after repeated use “mobilized” during withdrawal leading to “a slow taper” in the drug’s presence. He told attendees that “this is not dangerous, there’s no medication that’s necessary...it’s just the passage of time.”
    • Cannabis As Medicine (audio - 3m, video). Identifying the “potential therapeutic targets” for cannabis, Jackson indicated:
      • Cannabis use as a painkiller didn’t seem to lead to hyperalgesia, an increased sensitivity to pain, which he said had been associated with opioid painkillers. 
      • “Muscle spasticity” had been impacted by cannabis and could help multiple sclerosis.
      • Gastrointestinal disorders “like Crohn's disease” could be helped through “cannabinoid receptors on the gut.”
      • Cannabis had long been shown to “suppress nausea and vomiting” and was useful for “a variety of reasons” including cancer chemotherapy. Jackson noted that synthetic THC, branded as Marinol, wasn’t as popular because “you lose that entourage effect” elicited from “a more broad spectrum” cannabinoid and terpene profile.
      • He added that cannabis had been used for appetite stimulation as well as the treatment of post-traumatic stress disorder (PTSD) which was an allowed authorization under Washington’s medical cannabis laws.
  • Staff went over a guidance document created by NW PTTC and fielded questions about Jackson’s presentation.
    • Porter shared a guidance document developed for prevention practitioners to describe “state cannabis policies and regulations” in Alaska, Idaho, Oregon, and Washington (audio - 1m, video).
    • Jackson and Porter asked participants about “cannabis prevention strategies you are using in your communities” (audio - 2m, video). Responses included:
      • School outreach and education
      • Partnering with retailers and budtenders for education
      • Media campaigns and evidence-based programs
      • Education around vaping and cannabis
      • Parent workshops
    • The presenters took questions from participants throughout the session and at the very end:
      • Easley asked about “marijuana being different for some people versus other people,” with some casual daily users not seeing adverse consequences or increased salience. Jackson suggested people not conflate “regular use, even daily use, as necessarily problematic use, it’s what happens to an individual as a result of their use.” Put another way, “you don’t help people change by telling them that they're wrong” (audio - 2m, video).
      • Early in the presentation, Al-Amin wanted to know if there were beneficial uses, and Jackson responded “absolutely” (audio - 1m, video).
      • Easley asked about overdoses from edibles and whether there were “reversible antidotes.” Jackson replied that “the short answer is no.” Elaborating, he said the best approach for cannabis was to let it pass as it wouldn't be lethal, or better yet "start low and go slow" (audio - 1m, video).
      • DeVose asked about the “difference between cannabis and cannabinoids.” Jackson said one was the plant and “cannabinoids are what’s in it.” He also mentioned "Charlotte's Web," a cannabis cultivar developed for the high CBD content and used to treat a young girl’s epilepsy (audio - 2m, video).
        • The girl for whom the treatment was named, Charlotte Figi, passed away on April 7th at age 13 after being hospitalized with pneumonia, and “treated as a likely COVID-19 case.” Colorado’s Governor issued a proclamation "Whereas, on April 7th, 2020 Charlotte Figi passed away, having left the world with a life-changing story of overcoming adversity through courage and grace, impacting the lives of many millions whose wellness and dignity was in part made possible by Charlotte and the Figi family’s devotion to finding a therapy, the great and loving State of Colorado shall honor her life and encompass her journey through our continued dedication to unearthing solutions, discovering community strength, and embodying the love of Charlotte. Therefore, I... do hereby proclaim April 7 forevermore as Charlotte Figi Day in the State of Colorado."
      • Tempelaere wanted to know about cessation, particularly “why is it so hard to stop, even after several months of quitting?” Jackson responded that he asked patients what they believed the positive effects of cannabis were for them, often hearing relaxation, while additionally believing “it’s that down-regulation of impulse control.” If a cannabis user liked the plant and continued to associate with others using it, “it’s really hard for that person to say ‘no’ in the moment” (audio - 2m, video). 
      • Velez asked about cannabis dependence vs. addiction, and Jackson replied that “physical dependence would just be judged by whether or not the person developed tolerance.” Cannabis use disorder involved meeting other DSM-5 criteria besides tolerance (audio - 1m, video).
      • Scott inquired about research into cannabis’ impact on reproductive function and pregnancy. “The short answer is no,” Jackson answered. He said this was one of many “missing pieces of science that we’d all like to know a whole lot more” about to counsel pregnant women. “So, the safest thing we can tell” pregnant women using cannabis is “that she’s probably better off if she stopped” (audio - 1m, video).
      • Zamudio brought up cannabinoid concentrations in flower vs. concentrates. Jackson said THC potency tended to “top out at about 25 to 28% THC” while concentrates could be “50, 60, 80%...they’re called ‘concentrates’ for a reason” (audio - 1m, video).
      • Groomsmith asked to define “a few times a week” for cannabis use. Jackson said he “meant days,” and that “three times in one day is not the same thing as three days during a week.” However, there were too many variables and not enough research to say what frequency was safe, he asserted (audio - 1m, video). 
      • Warburton wanted to know more about Jackson’s earlier analogy about the 400 pound tomatoes, who laughed and said it was “a tribute to the ingenuity of cannabis farmers.” People who put that level of effort into cultivation and breeding techniques were all but guaranteed to reap larger, stronger crops, he noted. Jackson encouraged people to learn more through the resources and references in the presentation (audio - 2m, video).

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