January 2022 Issue
Psychoactive Plant Compounds
By KC Wright, MS, RDN
Vol. 24, No. 1, P. 40
What RDs Need to Know About Their Effects on Human Health and Behavior
Beyond the human and environmental health merits of plant-based eating, certain plants also contain psychoactive compounds that, when consumed, fit precisely into receptors in the brain and can alter our consciousness. Some of these plant chemicals have made a significant revival, such as psychedelic agents, once considered illicit mind-expanding drugs of the 1960s counterculture. This article considers the historical use and botany of psychoactive plants, recent research initiatives, the risks and benefits associated with their increased mainstream use, and what this may mean in the context of dietetics practice and when counseling clients.
In his latest book, This Is Your Mind on Plants, Michael Pollan, a notable author; professor at the University of California, Berkeley’s Graduate School of Journalism; and professor of the practice of nonfiction at Harvard, details his inquisition of drugs, plants, and humans through his passion for gardening and engagement in self-experimentation. The book title is a riff on the 1980s war on drugs campaign commercial called “This Is Your Brain on Drugs,” showing someone cracking open a fresh egg and dropping it into an extremely hot frying pan to sizzle and burn.
Pollan bases his book on three of the compounds that comprise each category of the broad spectrum of psychoactive plant chemicals—opium, a sedative; caffeine, a stimulant; and mescaline, a hallucinogen—and links their composition to human consciousness. In the book, he reflects on how plant compounds can help people identify their deepest human needs and aspirations, the operations of their minds, and their entanglement with the natural world.
Pollan began his illustrious career as a garden writer, based on his practices as a home gardener learning about the symbiotic relationship between plants and people. He considers plants to be tools of nature that, when crossed with intellectual curiosity and human ingenuity, give us the opportunity to change our consciousness. But why do plants have these molecules that can change the minds of animals? According to Pollan, “You have to wonder: what’s in it for the plants to devise and manufacture molecules that can pass for human neurotransmitters and affect us in such profound ways?”
Psychoactive compounds within plants have evolved by deterring both pathogens and predators, while these same chemicals can affect the brains and mental states of humans who ingest them. Defensive secondary metabolites of plants include some well-known psychoactive compounds such as caffeine, nicotine, cocaine, and morphine. Psychoactive substances act on the nervous system, affecting mental processes and behavior; for example, hallucinogens can distort reality, sedatives can induce calm or sleep, and stimulants can wake the mind.1 Pollan suggests that once humans realized the effect some plants can have, they began to expand their habitat and exploit them.
It’s well understood that most drugs come from plants. Plants produce alkaloids, bitter-tasting compounds meant to discourage pests from eating them, and if pests persist, the molecules can poison them. Plant alkaloids include potent pharmacologic drugs such as caffeine, morphine, and mescaline. These molecules offer humans the capability to boost alertness and attention, relieve pain, and stimulate the imagination, and perhaps much more will be determined as research progresses. RDs will need to have insight on these compounds and their impact on human health, especially since easing legal restrictions for some of them may make their use more commonplace among clients and patients.
Fifty years ago, the United States took a harsh approach to drug use and addiction by implementing the most severe policies and penalties. Yet in 2011, the Global Commission on Drug Policy released a critical report stating that “the war on drugs has failed, with devastating consequences for individuals and societies around the world.”2 Pollan asserts that society has taken a simplistic account of drugs, lumping them all together, which has barred people from objective consideration for potential physical and mental health uses of different substances.
Ironically, two of the most addictive plant psychoactive compounds—ethanol in alcoholic beverages and nicotine in tobacco—are legal drugs, with the latter being the leading cause of preventable death.3 When a person smokes a cigarette, nicotine reaches the brain within seven seconds, activating several neurotransmitters, some of which initiate pleasure, suppress appetite, or reduce tension and anxiety. While nicotine plays the addictive role in tobacco, it’s the complex mixture of chemicals produced by burning tobacco and its additives that lead to cancer, heart disease, and other illnesses.
The fermentation of plant sugars or starches produce ethanol, a central nervous system (CNS) depressant that reduces overall brain activity. Drinking alcohol stimulates the release of dopamine and endorphins that produce feelings of pleasure and satisfaction. Alcohol abuse can negatively affect the brain, heart, liver, pancreas, and immune system, while increasing the risk of certain cancers.
As mentioned, opium is one of the compounds within the broad spectrum of psychoactive plant chemicals. Opium has been used as a painkiller for thousands of years. It’s composed of elaborate molecules nearly identical to the molecules the human brain produces to confront pain and compensate itself with pleasure. It’s extracted from the common poppy flowering plant, Papaver somniferum, and is the key source for many narcotics, including morphine, codeine, and heroin.
P somniferum plants make poppy seeds that are legal and widely available from many seed catalogues. Poppies are thought to be native to the Mediterranean, as the Greeks and Romans have cultivated them for thousands of years. Poppies thrive in temperate climates but also can be grown in tropical regions.
In 1996, there were about 4,700 deaths from overdose on any drug. That same year, Purdue Pharma launched and marketed OxyContin (a synthetic opioid drug derived from the poppy plant) to physicians as safer and less addictive than other opiates, stating that it could benefit cancer and surgery patients as well as those suffering from arthritis, back pain, and workplace injuries. Through OxyContin prescriptions, thousands of people became addicted to opioids, eventually turning to the underground when they could no longer get or afford a prescription.4 As a result, the number of opioid overdose deaths has quadrupled since 1999; there were around 50,000 deaths in 2019 alone.5
Pollan claims that during his formative years, the war on drugs made him fearful of engaging with any illicit plants, but he reveals he eventually experimented with growing opium poppy in his Connecticut garden 25 years ago. He notes that it’s legal to buy poppy seeds and grow the flowers, but if you tried to extract opium from it, that would be illegal.
According to Pollan, whether poppy seed pods are grown or purchased, fresh or dried, they contain significant quantities of morphine, codeine, and thebaine, three of the principal alkaloids found in opium. Back then, he had written an essay for Harper’s Magazine called “Opium Made Easy,” but deleted the recipe he used to make opium as well as his experience after ingesting it. This self-censorship resulted from consultation with lawyers and facing both the risk of arrest and confiscation of his house, something he wasn’t willing to gamble as a young husband and father. This Is Your Mind on Plants includes the omitted sections of this essay due to less risk with transitioning legal and societal views on drugs.
To that point, in February 2021, Oregon passed a law to reflect a measure its citizens overwhelmingly voted on to make possession of small amounts of cocaine, opioids, LSD, and methamphetamine, among other drugs, punishable by a civil citation, similar to a parking ticket, and a $100 fine (waived with a health screening by an addiction recovery center).6 As the war on drugs is now widely recognized as a failure, Pollan notes that the opioid crisis has stamped a stigma on the opium flower and its medicinal properties. “What is true for the opium poppy is true for all medicines that plants have given us: they are both allies and poisons at once, which means it’s up to us to devise a healthy relationship with them,” he says.
Most dietitians reading this article regularly ingest the psychoactive plant compound 1,3,7-trimethylxanthine—that is, caffeine. Worldwide, it’s the most widely consumed stimulant, and it acts on the CNS to increase alertness and energy levels.7 People consume caffeine in many forms, most often as species within the genus Coffea (predominantly Coffea arabica)
and as the Camellia sinensis plant, commonly known as coffee and tea, respectively. Pollan traces coffee consumption back to 15th-century Africa, followed by the population of coffeehouses in the Arab world before its introduction into Europe during the 17th century that appeared to foster the Age of Enlightenment.
Coffea species are woody shrubs in the Rubiaceae family, native to the forest understory of the East African highlands. Although it’s grown in many rainy, warm climates of the world, the majority of coffee now is cultivated in South and Central America, with Brazil being the largest producer.
Tea was first cultivated in China thousands of years ago by monks who believed it was an important aid to meditation. C sinensis is a species of evergreen shrubs or small trees in the flowering plant family Theaceae, whose leaves and buds are used to produce white, yellow, green, oolong, or black tea. Tea is cultivated mainly in tropical climates with significant annual rainfall such as in India, Nepal, and China, as well as in parts of the United Kingdom mainland as clonal plants.
Pollan explains how caffeine serves plants as a pesticide, designed to keep other plants from growing around coffee and tea bushes. Meanwhile, bees are attracted to a plant’s nectar where they procure a small dose of caffeine that reminds them which plant to return to for more food. In essence, the plant trains the bees to pollinate them.
Pollan analogizes that, like bees, humans become trained to consume caffeine, which helps improve memory and makes them work harder and more attentively. He says caffeine mainly functions as a “tiny molecule that happens to fit snugly into an important receptor in the CNS,” blocking the neuromodulator adenosine, a psychoactive compound that has a depressive and sleep-inducing effect on the brain when bound to its receptor. Caffeine inhabits adenosine’s receptor sites, increasing levels of adenosine in the brain. After the liver removes the caffeine from circulation (as long as 10 hours post absorption), the concentrate of adenosine rebounds with its chemical action on the brain, leaving one feeling tired and perhaps sluggish. In response, most people consume more caffeine, demonstrating the common human dependence on this plant psychoactive.
Caffeine withdrawal and caffeine use disorder are recognized in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, as conditions for which further research is encouraged.8 As an adenosine receptor antagonist, caffeine activates the release of mainly excitatory transmitters, including dopamine, commonly seen in drugs of abuse. Caffeine also is a vasodilator and can be mildly diuretic. It temporarily raises blood pressure and relaxes the body’s smooth muscles, which may account for its laxative effect.4
On average, US adults consume 1 1/2 8-oz cups of coffee daily, which contains 135 mg caffeine. Many sodas contain caffeine, as do energy drinks, some of which have 200 mg or more of caffeine per serving. Chocolate contains caffeine, with the highest percentage of cocoa having the greatest amount of caffeine (eg, 25 mg/oz for dark chocolate with 70% cocoa solids).
Caffeine is quickly absorbed into the bloodstream, peaking within 15 minutes to two hours after ingestion. Food and nutrients consumed simultaneously can delay caffeine absorption. Heredity explains some of the differences in the effect caffeine can have among different people, while regular consumption can promote tolerance. A 1-g dose of caffeine can cause restlessness, irritability, nervousness, rapid heart rate, and tremors.9 Consuming 1.2 g or more of caffeine in one dose can be toxic, causing vomiting and convulsions, while a 10 to 14 g dose can be fatal. It would take about 100 cups of brewed coffee to equal 10 g of caffeine; toxic levels more often are due to caffeine pills or tablets.10
Over the decades, research has demonstrated both the health benefits and hazards of consuming caffeine. More recently, an umbrella review of the evidence across meta-analyses of observational studies and randomized controlled trials showed that coffee (when not consumed in excess) was associated with a probable decreased risk of breast, colorectal, colon, endometrial, and prostate cancers; CVD and mortality; Parkinson’s disease; and type 2 diabetes, while caffeine itself was associated with probable decreased risk of Parkinson’s disease and type 2 diabetes, but an increased risk of pregnancy loss.11 Sleep experts Pollan consulted (each of whom stated they avoid caffeine) explained how caffeine compromises quantity and quality of sleep. RDs can assess patients’ level of caffeine consumption to determine whether it may affect their health status.
In 1938, while investigating new pharmaceutical medications, a Swiss chemist synthesized lysergic acid diethylamide, more commonly known as LSD (or “acid” in slang). Lysergic acid is derived from ergot alkaloids caused by the fungus Claviceps purpurea, which grows on rye and other grains. It’s usually prepared by chemical synthesis in a laboratory and formed into a crystal.
In the 1950s, a group of pioneering psychiatrists used LSD as treatment for alcoholism and various mental disorders. London psychiatrist Humphry Osmond, MD, coined the term psychedelic, meaning “mind manifesting” and demonstrated that hallucinogenic drugs had therapeutic potential.12 Psychedelics act on receptors for serotonin, a neurotransmitter that affects mood. The premise of psychedelic therapy is that the drug confers a receptive state where a patient has the potential to consider both the past and future, which the therapist can guide for positive outcomes.13
The 1990s brought a rejuvenation of psychedelic medical research with the potential to meet treatment needs for depression and other diseases.14 Research on psychedelics has continued to flourish as evidenced by gifts totaling $17 million in 2019 to fund the launch of the Johns Hopkins University Center for Psychedelic & Consciousness Research. Along with research on brain activity, anxiety, and PTSD, current projects at Johns Hopkins include smoking cessation, Alzheimer’s disease, and anorexia nervosa.
What may be interesting to note is that most psychedelics are neither habit forming nor toxic, and there’s no lethal dose. However, they can be psychologically risky for people with schizophrenia and a family history of psychosis. The stimulant and psychedelic MDMA (3,4-methylenedioxymethamphetamine) commonly known as the drugs ecstasy or Molly (researched to treat PTSD) are derived from amphetamines and thus may present some risk of abuse.13,15
Psilocybin is a compound found in what are commonly referred to as “magic mushrooms,” which can alter consciousness and produce visual and auditory hallucinations. Mushrooms containing psilocybin include the genera Copelandia, Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, and Psilocybe. They’ve been depicted in Stone Age rock in Africa and Europe, most notably represented in the pre-Columbian sculptures and glyphs throughout North, Central, and South America. Many species are found in Mexico, Canada, and the United States that grow in meadows and woods in tropical and temperate regions. Magic mushrooms can be eaten in fresh or dried form, though gastrointestinal side effects are expected. They also can be steeped in tea or cooked into foods. Powdered psilocybin can be snorted or injected. It’s advised that individuals use extreme caution about the identity and safety of any mushroom they want to consume.
Researchers from Johns Hopkins University School of Medicine gave adult subjects with major depression two doses of psilocybin under clinical guidance and monitoring. Results showed that psilocybin along with psychotherapy dramatically reduced symptoms for a month, with one-half of the subjects in remission from the depression at follow-up. The degree to which the effect on depression persisted was about four times greater compared with clinical trials of traditional antidepressant medications.16
Some in the psychedelic research field anticipate that psilocybin with psychological support will become an early option in the treatment of depression, while others suggest its use requires medical justification, and still others think it should be available for recreational use as in the case of alcohol and, increasingly, cannabis.14 In fact, several cities and states across the United States are in the process of legalizing or decriminalizing psilocybin for therapeutic or recreational purposes.13
In This Is Your Mind on Plants, Pollan details his relatively recent interest in the psychedelic mescaline found in peyote cactus and San Pedro cactus. The peyote cactus is found only in limestone soils of the Chihuahuan desert of southern Texas and northern Mexico, while the San Pedro cactus is native to the Andes but now is also cultivated in other parts of the world, including California. Indigenous populations have used both cacti for more than 6,000 years for sacramental healing, often to treat alcoholism or other illnesses. San Pedro cultivation—but not extraction of its psychedelic compound, mescaline— is legal, whereas peyote is entirely illicit, except for the some 250,000 members of the Native American Church, who have the constitutional right to use peyote per the American Indian Religious Freedom Act Amendments of 1994.
Pollan strongly cautions that individuals should use psychedelics only under certain conditions: with intention, reverence for the drug and experience, and the assistance of a trained guide. He also advises that the closer the drug dose is to the whole plant, the milder and safer the compound will be.
Pollan suggests psychedelic drugs can benefit us “and occasionally our culture by stimulating the imagination and nourishing our creativity.”
Consider New Perspectives
Humans have a longstanding, symbiotic relationship with plants that can provide nourishment, beauty, and the ability to alter consciousness. Renewed and promising medical research in plant psychoactive compounds to treat addiction, depression, and other diseases, along with Pollan’s latest book, offer RDs the opportunity to consider a new or different perspective on the benefits of plants. According to Pollan, similar to food, a psychoactive drug is inert and ineffective without a human brain. In sharing his research, he hopes to enlighten others on beliefs about drug abuse and addiction. Pollan believes there’s much people can learn from the traditions of certain Native American tribes, and that there’s a way to have a safe and healthy relationship with plant psychoactives. In 2020, Pollan cofounded the UC Berkeley Center for the Science of Psychedelics to conduct research, using psychedelics to investigate cognition, perception, and emotion and their
biological bases in the human brain.
— KC Wright, MS, RDN, is a research dietitian advocating for sustainable foods and planetary health at wildberrycommunications.com.
In today’s global society, diverse populations from a wide range of genetic and cultural backgrounds integrate throughout the world and into the practices of dietitians.
The following tips may be helpful when consulting with clients and patients who may be using psychoactive compounds—with or without medical supervision.
• Treat clients and patients as whole beings, emphasizing the benefits of nutrition for mind and body.
• Avoid stigmatizing addiction. It’s an illness that requires therapeutic treatment.
• Plant psychoactives can be both allies and poisons. As Michael Pollan, author of This Is Your Mind on Plants, suggests, it’s up to humans to have a healthy relationship with them.
• Practice cutting out caffeine for a week or month to understand what it’s like to experience caffeine withdrawal.
• Share knowledge of sources of caffeine in food and beverages.
• The FDA considers 400 mg caffeine, equivalent to about four or five measured cups of brewed coffee, to be a safe amount for healthy adults to consume daily. Pregnant women should limit their caffeine intake to less than 300 mg daily, or about two to three cups of coffee, according to the 2020–2025 Dietary Guidelines for Americans.
• The American Academy of Pediatrics recommends that children under age 12 not consume any food or beverage containing caffeine. In children aged 12 and up, caffeine should be limited to no more than 100 mg daily, the amount in two 12-oz cans of cola soda.
• Caffeine also may be added to analgesics to provide faster and more effective relief. Consider also that caffeine can interact with various medications.
• Evaluate new, opportunistic products on the market, such as Psychedelic Water, for purity, safety, and efficacy.
1. Alrashedy NA, Molina J. The ethnobotany of psychoactive plant use: a phylogenetic perspective. PeerJ. 2016;4:e2546.
2. Global Commission on Drug Policy. War on drugs: report of the Global Commission on Drug Policy. http://www.globalcommissionondrugs.org/wp-content/uploads/2017/10/GCDP_WaronDrugs_EN.pdf. Published June 2011. Accessed September 30, 2021.
3. Find help: ATOD. Substance Abuse and Mental Health Services Administration website. https://www.samhsa.gov/find-help/atod. Updated October 25, 2021.
4. Pollan M. This Is Your Mind on Plants. New York, NY: Penguin Press; 2021.
5. Understanding the epidemic. Centers for Disease Control and Prevention website. https://www.cdc.gov/opioids/basics/epidemic.html. Updated March 17, 2021. Accessed September 30, 2021.
6. State of Oregon, Legislative Policy and Research Office. Measure 110 (2020). https://www.oregonlegislature.gov/lpro/Publications/Background-Brief-Measure-110-(2020).pdf. Published December 9, 2020.
7. Clark I, Landolt HP. Coffee, caffeine, and sleep: a systematic review of epidemiological studies and randomized controlled trials. Sleep Med Rev. 2017;31:70-78.
8. Meredith SE, Juliano LM, Hughes JR, Griffiths RR. Caffeine use disorder: a comprehensive review and research agenda. J Caffeine Res. 2013;3(3):114-130.
9. Caffeine for the sustainment of mental task performance: formulations for military operations. NCBI Bookshelf website. https://www.ncbi.nlm.nih.gov/books/NBK223808/. Published 2001. Accessed September 30, 2021.
10. Caffeine. Harvard T.H. Chan School of Public Health website. https://www.hsph.harvard.edu/nutritionsource/caffeine/. Accessed September 29, 2021.
11. Grosso G, Godos J, Galvano F, Giovannucci EL. Coffee, caffeine, and health outcomes: an umbrella review. Annu Rev Nutr. 2017;37:131-156.
12. Costandi M. A brief history of psychedelic psychiatry. The Guardian. September 2, 2014. https://www.theguardian.com/science/neurophilosophy/2014/sep/02/psychedelic-psychiatry. Accessed September 30, 2021.
13. Tullis P. The rise of psychedelic psychotherapy. Nature. 2021;589:506-509.
14. Carhart-Harris RL, Goodwin GM. The therapeutic potential of psychedelic drugs: past, present, and future. Neuropsychopharmacol. 2017;42(11):2105-2113.
15. Psychedelic drug MDMA may reawaken ‘critical period’ in brain to help treat PTSD. Johns Hopkins Medicine website. https://www.hopkinsmedicine.org/news/newsroom/news-releases/psychedelic-drug-mdma-may-reawaken-critical-period-in-brain-to-help-treat-ptsd. Published April 4, 2019.
16. Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2021;78(5):481-489.