Psychedelics and the Opioid Crisis

Introduction

Third Wave supports the measured, practiced use of psychedelic substances like psilocybin, DMT, and LSD for therapeutic and creative reasons where it is legal to do so. However, these are illegal in the United States, categorized as Schedule 1 substances by the Drug Enforcement Agency. This means they are deemed to have a high potential for abuse, pose severe safety concerns, and have no medical use.

Despite that designation, Third Wave challenges those statements about psychedelics. And, the group advocates for the regulated use of all substances to be legal in the United States. In doing so, it is important to acknowledge that not all substances affect people in the same ways.

Today, the high rates of abuse and related deaths due to heroin and other opioid-based substances have reached epidemic proportions. In advocating for the legal, regulated use of all substances, we want to highlight the differences between psychedelics and opioids. In doing so, we can also explore how regulations can play a role in promoting safe, responsible substance use.

The proven and potential benefits of using psychedelics responsibly far outweigh the risks. This is a point proven literally throughout history, even as current U.S. law reflects otherwise.

Many opioids also have proven medical benefits, reflected in the legality of opioid-based medications. However, overall the risks of opioid use are much higher than psychedelic use, even when used responsibly and as directed by medical professionals.

We believe it is important to highlight the differences between psychedelics and opioids while responsibly advocating for legal, regulated use of all substances. In doing so, we can also explore how existing and potential regulations can play a role in promoting safe, responsible substance use.

Overview of the opioid crisis in the U.S.

National statistics paint an unmistakable, and grim, picture of how damaging widespread opioid abuse has become, and how quickly it reached epidemic proportions. Although heroin abuse, in particular, was once considered a social problem mostly constrained to urban areas, it spread over the past decade to suburbs and outlying counties.^[1]

The number of heroin-related deaths nationwide rose 248 percent from 2010 to 2014.^[1]  8,200 people died of heroin-related causes in 2013, ^[2] while 10,575 died the next year.^[1] In 2014, 18,893 others died in 2014 from opioids other than heroin.^[3]

Along with heroin, the epidemic also includes prescription opioid-based medications including hydrocodone (Vicodin), oxycodone (Percocet), oxymorphone (Opana), morphine, and codeine.^[4]

The synthetic opioid fentanyl is also becoming an increasingly deadly drug. Much stronger than heroin, it leads to more overdoses among even experienced users. In the northeast region of the country, where heroin is often sold in white powder form as opposed to black tar, fentanyl can be mixed into a bag without the user knowing.^[1]

Just in Pennsylvania in 2016, there were 4,642 fatal drug overdoses — 13 people a day. Philadelphia alone had 907 deaths. Opioids were implicated in 85 percent of those deaths.^[5]

Nationwide, there were 42,249 deaths due to opioids that year.^[6] The number shows a sharp rise: The rate of deaths due to overdoses from opioids other than methadone increased around 18 percent annually from 1999 to 2006 and then remained relatively static until 2013. Then, it increased by 88 percent every year from 2013 through 2016.

This increase was impactful enough to depress the overall life expectancy in the U.S. from 78.6 to 78.5 years. This is the first time since the early 1960s that life expectancy has dropped over a two-year period.^[7]

The increase in heroin use, which is often administered intravenously despite rises in other methods, has also fueled a rise in cases of the Hepatitis C virus (HCV). Reported HCV cases increased 294 percent from 2010 to 2014, with the largest increases among young people who inject drugs.^[8]

Many factors contribute to the current opioid crisis. Widespread prescribing, use, and abuse of controlled prescription drugs or CPDs, such as Vicodin, Oxycontin, and Percocet over the past two decades fueled an increasing market for heroin.^[1][9]

Sales of these nearly quadrupled from 1999 to 2014 in the U.S., although there was no corresponding increase in the amount of pain reported by Americans.^[10] This increase was concurrent with a sharp rise in overdoses due to heroin and other opioids.

Some 45 percent of heroin users were also addicted to a prescription drug, making its abuse the strongest risk factor for heroin addiction.^[2]

CPD abusers often seek out heroin because it’s less expensive and easier to obtain.^[11] In 1981, one gram of pure heroin retailed for $3,260 in 2012 dollars. By 1999 the same amount retailed for $622, similarly adjusted for inflation.^[1] Since then, the price has hovered around $500.^[1]

Meanwhile, the percentage of purity in any given batch peaked in the mid-’90s but is still significantly higher than it was before then. More pure heroin led to more people snorting or smoking the drug. That made it appealing to more people who wouldn’t have considered injecting a drug; today it is common for new users to inhale.^[1]

Finally, availability played a role. Approximately 20 years ago, Mexican traffickers increased their production and distribution of heroin, a market previously held by their Colombian counterparts. To avoid detection, they moved many of their operations out of cities and into suburban areas. This change increased distribution and widened the user base by tapping new geographical areas.^[1]

Opioids throughout history

The word “opiate” refers to any drug derived from opium, while the all-encompassing “opioid” refers to natural and synthetic opiates.^[12] Opium and opiate-based substances have been used since at least 3,400 BC.^[13]

Sumerians referred to the poppy plant, from which opioids are derived, as the “joy plant.” They passed knowledge of cultivating it to the Assyrians, the Babylonians, and later ancient Egyptians. It spread to Persia and India via Alexander the Great around 330 B.C., and to China around 400 A.D. thanks to Arab traders. ^[13]

For centuries, opium was used both for recreational and medicinal purposes. The Portuguese began smoking opium in the 1500s; people in Persia and India began drinking and eating opium mixtures in the next century. The Dutch introduced the Chinese to smoking opium through a tobacco pipe in 1700.^[13]

Opioid-based medications have been used to treat everything from pain to coughs to diarrhea. In modern times, they’ve been used to treat acute pain and, since, the 1990s, increasingly for chronic pain despite there being little evidence pointing to their long-term effectiveness.^[14]

In the early 1800s, a German pharmacist created the derivative morphine, while English literary figures around the same time began using opium strictly for recreational use. The autobiographical Confessions of an English Opium-eater, published in 1821, documented opium addiction, while commercial production of morphine kicked off in 1827.^[13]

In the U.S., knowledge that opium and its derivatives caused addiction and social problems was well-known and reported by the 1850s. The next decade would see thousands of servicemen become addicted to opiates as they were administered intravenously for wounds during the Civil War. Experts at the time believed using the then-new hypodermic needles would prevent addiction.^[14]

Heroin began as a “wonder drug” that was more effective than codeine in treating respiratory diseases and without the side effects of morphine.^[13] The Bayer Company began producing on a  commercial scale in 1898; by 1902 medical journals argued that heroin withdrawal was equal to that of morphine. By 1903, heroin addiction rose to “alarming rates.” ^[13]

The U.S. outlawed opium imports in 1909. The Harrison Narcotics Act of 1914 required all physicians and pharmacists to register and pay a tax if they prescribed narcotics, and the government then banned all narcotics sales in 1923.^[13] Heroin was deemed a Schedule One drug when the U.S. passed the Controlled Substances Act of 1970.

Psychedelics throughout history

People’s experiences using naturally-occurring psychedelics predates written history, with evidence of early human cultures using them in rituals and other socio-cultural contexts.^[1]

Radiocarbon dating supports the theory that Native Americans used the plant-based peyote as far back as 5,700 years ago. Other evidence shows Native Americans using it specifically as a medicine stimulant and ceremonial medium since at least 100 B.C., despite Christians banning its use in 1620.^[15]

People in ancient India used a substance known as “Soma,” and researchers believe that a secret, all-night ceremony existed outside of Athens, Greece, for some 2,000 years that involved a psychedelic brew called “Kψkeov.” ^[16]

Ayahuasca, whose active ingredient is DMT, has been a part of the practices of two Brazilian churches for centuries.^[16] Psilocybin mushrooms (also known as “magic mushrooms” or “shrooms”) have a history of shamanic, healing, religious, and divinatory use among the Mayan, Aztec, and Olmec tribes in pre-Columbian Mesoamerica.^[16]

More recently, a 2013 study estimated that 30 million people worldwide have used LSD, psilocybin, or mescaline,^[17] even though they became illegal in many countries in the late ‘60s and early ‘70s. The change in legality was in large part driven by the United States, where the government believed that the then-current drug culture was fueling anti-war attitudes during the Vietnam War and a general rejection of societal norms.^[16]

When the U.S. passed the Controlled Substance Act of 1970, it relegated LSD, psilocybin, and other psychedelics to Schedule 1 substances. The law made it difficult for scientists to continue studying how psychedelics worked and to identify their potential benefits.^[16]

However, psychedelics such as LSD and MDMA had rich histories of therapeutic use by the time they were made illegal:

“Many people remember vaguely that LSD and other psychedelic drugs were once used experimentally in psychology, but few realize how much and how long they were used. This was not a quickly rejected and forgotten fad. Between the 1950s and the mid-60s, there more than 1,000 clinical papers discussing 40,000 patients, several dozen books, and six international conferences on psychedelic drug therapy. It aroused the interest of many psychiatrists who were in no sense cultural rebels or especially radical in their attitudes.”^[15]

How psychedelics and opiates work — and how they’re different

Pharmacologically, psychedelics and opiates work in very different ways. This accounts for them producing different effects and having different risk levels pertaining to addiction and physical health.

Put basically, opioid use limits pain, produces pleasure, and suppresses the respiratory system by exploiting an existing system in the body. The body naturally produces endogenous opioids that bind to receptors. These do essentially the same things as ingested opioids but do not occur naturally in large enough quantities to produce significant pain reduction, euphoria, or respiratory depression.^[4]

Ingested opioids, however, attach to those same receptors throughout the body. In these quantities, they produce a feeling of pleasure and significantly reduce the perception of pain.^[4]

They also bind with dopamine receptors in the body. Dopamine is a neurotransmitter, essentially a chemical messenger that binds to receptors throughout the brain. It’s produced in the base of the brain and creates a pleasurable feeling when it’s released.

Dopamine is linked to the brain’s reward system, often released when people engage in activities necessary for survival such as eating, exercise, or sex. This shapes behavior by motivating a person to do these things repeatedly.^[18]

Finally, there is a toxicity level to opioids: ingest enough, and the body will stop working.^[12]

While much is still unknown about how psychedelics work, the classic serotonergic hallucinogens such as LSD, psilocybin, and DMT, largely produce their effects by binding to and activating serotonin in the brain’s 5HT-2A serotonin receptors.^[16]

Like dopamine, serotonin is a neurotransmitter but acts in different capacities. Serotonin is involved in nearly every human behavior from appetite to emotions, to cognition and mood. It appears to modulate the “tone of nervous system activity,” thus having a general effect on behavior.^[19]

Binding of serotonin to its receptors creates spontaneous neuronal excitation, meaning neurons are activated, which produces overwhelming excitation, or stimulation, of the cerebral cortex.^[16] This is the part of the brain associated with everything from auditory and visual processing to reasoning, emotions, and problem-solving.^[20]

Psychedelics also break down naturally-occurring barriers in the brain.

Ordinarily, regions of the brain known as hubs each have plenty of neuronal communication occurring inside them, with limited communication connecting them to other hubs.^[21]

When those barriers break down, communication then increases across the brain as neurotransmitters can follow many more paths than before. As the substance wears off and the hubs become segregated again, the state of universal connectivity also disappears. ^[21]

Ultimately, this brain activity results in experiences of unity, blissful states, spiritual experiences, insightfulness, feelings of disembodiment, impaired control and cognition, anxiety, and complex and elementary imagery.  It also is responsible for auditory and visual synesthesia, where people perceive sounds as visual images, and “changed meaning of precepts,” where people perceive normal “rules” or common ideas differently than usual.^[16]

For more on the ability of psychedelics to expand consciousness, read our article on the default mode network.

For humans, there are no known toxicity levels for “classic” psychedelics such as LSD and psilocybin. While sometimes listed under the general “psychedelic” umbrella, MDMA does have physiological toxicity – however, MDMA is physiologically very different from classic psychedelics and is more accurately classified as an amphetamine. [22]

Risks and addiction with opioids

Despite most psychedelics and opiates like heroin being classified as Schedule I drugs, there are major differences between each one’s potential for addiction.

Today, an important term when talking about addiction is “substance use disorder. (SUD)” It’s the term used by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) to describe “a cluster of cognitive, behavioral, and physiological symptoms” that indicate a person continues using a substance despite the presence of problems related to that substance.

SUD exists on a spectrum and is diagnosed using 11 criteria. These include:

• Taking more of a substance, or taking it for longer periods, than intended;
• An inability to cut down on or cease using a substance;
• Withdrawing from activities or hobbies to use the substance;
• Wailing to live up to responsibilities due to substance use;
• Developing tolerance to, and withdrawal symptoms from, the substance.

^[23]

People showing two or three of these criteria, or symptoms, have mild substance use disorder. Those with four or five symptoms are classified as moderate. Severe substance use disorder, commonly considered addiction, is considered present when a person shows six or more symptoms.^[22]

The risks of addiction between opioids and psychedelics differ greatly. In terms of SUD symptoms, this occurs significantly in three categories: withdrawal, dependence, and tolerance.

When a person uses opioids repeatedly, the substances inhibit the body’s natural production of opioids. Regular use leads to withdrawal symptoms when the body doesn’t produce enough endogenous opioids to maintain its basal levels.^[4]

Meanwhile, the body begins to establish a tolerance to the opioids through repeated use as the brain becomes desensitized to the natural opioid system. It then requires more to get the same results.^[5] The risk of overdose increases as more and more opioids in the body increasingly repress the respiratory system to the point of failure.^[24]

Opioid dependence is also largely driven by its effect on dopamine production and release. Like other addictive drugs, opioids target the brain’s “reward system” by flooding it with dopamine. The more the person uses it, the more the brain associates opioid use with natural, essential behavior.^[25]

Exploitation of the dopamine system like this is “a pharmacology that appears essential for nearly all drugs that can engender dependence.” It leads to what’s commonly referred to as a “rewiring” of the brain.” ^[16]

“When addiction takes over, a person’s ability to exert self-control can become seriously impaired. Brain imaging studies … show changes in areas of the brain that are critical for judgment, decision-making, learning, memory, and behavior control.” ^[25]

By contrast, there is no evidence that psychedelics lead to dependence or withdrawal. This is possibly because psychedelics bond with serotonin rather than dopamine receptors, and serotonin is not directly involved in the brain’s habit-forming and reward systems like dopamine.

While some psychedelics may have a small effect on the dopamine system, a 2006 study using neuroimaging found no changes in reward-related regions of the brain.^[26] They do not produce physical withdrawal symptoms, and tolerance and dependence are virtually absent with psychedelic use. Although a few substances, such as LSD, produce short-term tolerance, this wears off in a few days — not long enough to create dependence.^[16]

Meanwhile, characteristics of substances themselves affect how likely a person is to develop a dependence on them. How quickly the drug affects the brain, the degree to which it affects it, and the intensity of the rush upon initial exposure all play roles.^[23]

In particular, the intensity is affected by how a person takes the substance. Inhalation, an increasingly common method for heroin, is the fastest, followed by intravenous use. Ingestion, most common for psychedelics, is third.^[23]

According to John Kelly, director of MGH Recovery Institute, a nonprofit research group associated with Massachusetts General Hospital & Harvard Medical School and an associate professor of psychiatry at Harvard University, the possibility of consequences — bad things that can happen to a person as a result of substance use — is also important.

When there are no immediate consequences to substance use, a person is more likely to continue using it until they become dependent on it. This is, in part why opioids are potentially more addictive than alcohol, for instance, noted Kelly. Since people using opioids are generally sedated, they’re less likely to do something harmful or dangerous while under the influence.

“Opioids don’t induce blackouts or make people get into fights,” he said in an interview with Third Wave. “That doesn’t have a curbing effect on behavior.”

Finally, the longer a drug produces effects, the longer a person often goes without using it again or experiencing withdrawal symptoms. This puts psychedelics in contrast to substances like heroin, or crack cocaine, or methamphetamine, which cause dopamine levels to increase quickly and exponentially to produce a “rush.” Many of these substances wear off much quicker than psychedelics.

These factors add up to significantly different usage patterns for opioids and psychedelics, according to Kelly.

“Psychedelics haven’t been studies that much, but they tend not to be misused in the same way. People use them, especially LSD, sporadically. It’s a very profound, versus addictive, experience,” he explained.

A psychedelic, Kelly continued, “dramatically alters consciousness in the short term, but it’s not a substance people tend to take every day or develop a tolerance to.”

The benefits and risks of psychedelics

A growing number of modern studies on classic serotonergic hallucinogens show the potential for psychedelics to address mental disorders. Studies show their effects not only on addiction, but also anxiety, depression, and post-traumatic stress disorder, or PTSD — conditions that are often present in people also suffering from addiction, or substance abuse disorder.^[27][28][29]

Much of the research has centered on single doses of psilocybin and LSD, with some studies on ayahuasca, MDMA, and other substances. Just a few of many recent findings include:

• Psilocybin can produce “immediate, substantial, and sustained improvements in anxiety and depression” in cancer patients. The results of a single dose are stronger when combined with psychotherapy.^[30]
• Patients with substance abuse disorder, depression, and anxiety showed better therapeutic outcomes after a dose of psilocybin.^[31]
• Separate studies of LSD and MDMA showed that the feelings of happiness, well-being, closeness to others, trust, and openness these substances produce in subjects can facilitate psychotherapy.^[31]
• A 2017 review of recent clinical studies on psychedelics noted that use of classic hallucinogens in controlled settings is associated with lower suicidality, fewer mental health problems, lower psychological distress, and long-lasting positive effects.^[31]
• Psychosocial treatment using psilocybin produced decreased craving in ten volunteers with alcohol dependence, and improvements in drinking behavior and self-efficacy, or the belief in one’s own ability to complete a task. A similar treatment without psilocybin did not produce any significant results.^[32]
• A retrospective analysis of six clinical trials, including control groups, from 1943 to 2010 concluded that various treatment programs using a single dose of LSD were associated with a decrease in alcohol misuse.^[17]
• Smoking abstinence rates were greater after six months for 15 subjects who received up to three doses of psilocybin during a 15-week cessation program, than for typical pharmacological and behavioral cessation programs.^[33]
• An ayahuasca study published in 2015 demonstrated the substance’s “significant and quite impressive acute antidepressive effects” across groups of people with varying levels of depression. ^[34]
• In a 2012 study, 19 subjects with chronic, treatment-resistant PTSD received MDMA-assisted psychotherapy. Of the 16 people who completed all the long-term follow-up measures over 74 months, 14 maintained “statistically and clinically-significant gains in symptom relief.”^[35]  Results like these renew calls for MDMA to be used in therapy for its “unique pharmacological properties that … assist trauma-focused therapy,”^[36] especially for PTSD which is often a chronic condition for which resistance to treatment “remains high.”^[37]

Meanwhile, multiple studies have shown a lack of chronic or long-lasting negative effects of psychedelics. These studies include:

• Analysis of data drawn from the National Survey on Drug Use and Health spanning 2001 to 2004 did not reveal any associations between the lifetime use of LSD and an increased rate of any mental health outcome. Several cases showed a correlation between the use of psychedelics and a lower rate of mental health problems. ^[17]
• Researchers studied the cognitive functions of 61 members of the Navajo Native American Church, which uses peyote in its rituals. The Rand Mental Health Inventory and ten standard neuropsychological tests showed no significant mental deficits, nor any association between peyote and neuropsychological performance.^[38]
• A 2004 study in which participants received varying quantities of psilocybin showed no evidence of the substance being hazardous to somatic, or bodily rather than psychological, health. ^[39]
• A group of 22 subjects who used ayahuasca at least 50 times in the two years before participating in the study, along with a control group of 22 other people, were assessed using three neuropsychological tests and magnetic resonance imaging to examine the brain. The ayahuasca users did not show any increased signs of mental disorders than the control group, nor did they score any lower on the tests. The ayahuasca users scored significantly better than the control group when it came to “harm avoidance” and “self-transcendence.”^[31]

There are, of course, some risks associated with psychedelic use. While under the effects of a psychedelic, a user’s judgment is impaired, which may lead them to do things they wouldn’t normally do. Improper use of these substances, without adequate support, could potentially lead to dangerous behaviors.^[16]

High doses of psychedelics can lead to vascular problems due to serotonin’s association with vascular smooth muscle contractions and other circulatory functions. Some also cause increases in blood pressure. Psilocybin, even in controlled settings, can cause headaches. ^[16]

There is also evidence that heavy use of MDMA — which, again, is not a classic psychedelic but is sometimes categorized with them —- can potentially lead to heart disease. Studies show that using MDMA multiple times a week can lead to damaged heart valves. In extreme cases, it results in valvular heart disease. ^[40][41]

Reports of anxiety or other temporary negative mental states that required medical intervention were not difficult to address, nor did they persist after the substances wore off. Researchers also note the use of proper set (meaning mental state or expectations) and setting (environment) when taking psychedelics to facilitate a positive experience.^[16]

Some, like ayahuasca and ibogaine, cause vomiting. There is also concern by researchers about toxicity levels in ibogaine. While not common, high doses have resulted in seizures and cardiac dysrhythmias, and in very few cases, death. Some researchers have called for a moratorium on its use in treatment until further studies determine a safe dosage.^[42]

Ibogaine aside, these are considered low-risk adverse effects, especially as they can be mediated by responsible usage and in controlled settings.^[43] Safety guidelines state that patients should not be given psychedelics to use at home, be screened for mental illness and physical fitness, and receive hours of psychotherapy before official use.^[21]

Ultimately, modern LSD studies have not yielded any severe adverse reactions, apart from relatively few isolated incidents. This reinforces the view that the substance is relatively safe when it is used according to safety guidelines and in medical settings.^[31]

Many instances of severe adverse reactions, from vision problems to renal failure, often occur when other substances are present in the body, or the substance the person has used turns out not to be what they thought it was. This makes it difficult to determine what exactly caused the reaction.^[16]

It’s also notable, then, that even the most severe horror stories from the height of LSD use in the 1960s include other factors. In its chapter on adverse effects, the 1979 book “Psychedelic Drugs Reconsidered” notes that actual cases of suicide, murder, or accidents due to psychedelics were rare, despite “how eager the press was for this type of material.”^[15]

In many cases, incidents occurred either weeks or months after psychedelic use or involved other factors like existing mental instability or use of other substances.^[15] Virtually none of the documented episodes occurred within the established medical guidelines for therapeutic psychedelic use.

The case of Stephen Kessler outlined in the 1966 Time Magazine report “The Dangers of LSD,” for instance, notes that he admitted to being “flying for three days on LSD” before being charged with homicide.^[44] During his trial, he admitted to taking LSD five times, and not for a month before the murder. In the days leading up to the homicide, however, he had consumed barbiturates and laboratory alcohol and was judged a chronic paranoid schizophrenic.^[15]

The researchers do not seek to whitewash the potential for severe adverse effects from LSD or other psychedelic use, noting handfuls of documented incidents. However, they note:

“More easily available and commonly used drugs like alcohol, amphetamines, barbiturates, and phencyclidine create more danger of murder, suicide, and accidents than LSD, because they are taken much more casually and because they are more likely to provoke physical activity while impairing judgment and coordination. There are people for whom no powerful psychoactive drug is safe, and the dangers in using psychedelic drugs are far from negligible. But the significance of occasional incidents should not be overestimated.”^[15]

The potential for psychedelics to address the opioid epidemic

Over the past decade, there has been a resurgence of research into the potential use of psychedelics to treat addiction.

Most of the studies focus on nicotine and alcohol rather than opioids for a host of reasons. More people are affected by those than opioids, while people with alcohol or nicotine addictions tend to have better support networks than those battling heroin addiction. This makes them safer test subjects should they relapse.ways to treat alcohol or nicotine addictions, then, would also apply to addictions to opioids and other substances.

However, there is still research on psychedelics and opioids specifically. The plant-based psychedelic ibogaine, in particular, is being studied for its unique effects on opioid dependence and, unusually, on physical withdrawal symptoms. Two studies funded by the Multidisciplinary Association for Psychedelic Studies, or MAPS, and published in 2017 document treatments in Mexico and New Zealand.

In the Mexico study, subjects that had unsuccessfully attempted treatment for oxycodone and heroin addictions were given one dose of ibogaine while detoxing from opioids and observed five times in the 12 months after the treatment ended. They scored significantly low on subjective scales measuring their withdrawal symptoms and severity of their addiction after 30 days and reported zero opioid use in that time. Many continued to abstain or reduce their opioid use over the entire 12-month period.^[46]

Ibogaine similarly reduced withdrawal and craving symptoms when administered once during detox treatment in New Zealand. Of the 14 subjects studied, 13 showed reduced withdrawal symptoms and either abstained from opioid use or greatly reduced their intake, over the following 12 months.^[47]

This was, however, a study in which one participant passed away. According to the study, two investigations pointed to “failed duty of care” by the treatment provider, while forensic evidence suggested the death was most likely “related to ibogaine ingestion and most probably related to a cardiac arrhythmia.”^[49]

This, however, supports the notion that such risks are mitigated by following clinical guidelines. Researchers continue to study the substance to determine non-toxic levels for human use.

Meanwhile, according to these and other independent studies, ibogaine may offer a path for further neurobiological research and potential prototypes for “an interesting prototype” for new drugs to combat addiction. This is because it works at a molecular level to modify opioid withdrawal.^[48]

Unlike most compounds, including opioids and other psychedelics, which bind to a receptor on the outside a cell membrane, ibogaine binds on the inside. This is “something no other naturally occurring molecule is known to do,” and leads researchers to believe ibogaine may hold the key to new addiction-fighting tools.^[47]

In June 2017, MAPS outlined reasons for the federal government to fund clinical research of ibogaine’s potential to fight opioid addiction, noting its risks but also highlighting its benefits compared to other treatments.

In comments submitted to the President’s Commission on Combating Drug Addiction and the Opioid Crisis, the group noted:

“Currently-used treatment methods for opioid dependence … stimulate and satisfy an addict’s opioid receptors and typically require an extended period of use to gradually wean an addict from dependence. In contrast, ibogaine appears to reset addicted receptors in the brain … Unlike buprenorphine and methadone which are known to perpetuate dependence, ibogaine has no history of being addictive and presents a very low potential for abuse … To be sure, ibogaine requires further study to determine its safety.”^[45]

Funding is only one of the challenges facing psychedelics research. There’s also the public perception of psychedelics and their use.

“One question we’re working on is whether psychedelic therapy can be an effective treatment for addiction. It’s really not about a neurotransmitter or a single system,” explained Brad Burge, director of strategic communications for MAPS, in an interview with Third Wave.

Ibogaine treatment, for instance, may go a long way in reducing withdrawal and cravings, but that’s just a first step.

“What makes a difference is lasting care, lasting therapy, people making changes in their lifestyle. It requires psychological, financial, and emotional support,” said Burge.

There’s a significant difference in therapeutic use versus people using psychedelics recreationally or even spiritually — there’s a fine line between the two, notes Burge — on their own.

“In most contexts where they’re accepted, like nightclubs, raves, or EDM festivals where they’re even encouraged, there are distractions everywhere,” he said. “Flashing lights, loud sounds, it’s almost as if people are trying to avoid paying attention to any real emotional material that might come up.”

In therapy, Burge continued, “People come in rested at 10 a.m., and they are in a therapist’s office for the entire day. They stay the night in a clinic in a comfortable bed, and someone drives them home. There are follow-up phone calls, another visit a few days later. They get all the support they need.”

With all the new research, it’s tempting to think researchers see psychedelics as panaceas for mental illnesses. But that would be going down the same road as opioids, Burge notes, similar to opiates being lauded a miracle cure for battle wounds in the Civil War, and heroin being promoted as a cure-all by Beyer in the early 20th century.

But, he argues, psychedelics went through that phase in the ‘60s and ‘70s, when use was widespread. An upside of all that use, combined with the decades of clinical use preceding it, is that researchers know a lot about the substances and their risks. An example of this is MDMA.

“In some ways, we know more about MDMA than currently-approved [antidepressant medications] because it’s been around longer,” he said. At the most, clinical trials before FDA approval can identify maybe the one-in-100,000 side effect. Thanks to decades of MDMA use, “If there was a one-in-a-million side effect, we would know it by now. We’ve seen usage. We know the risks.”

Burge notes that the National Institute of Drug Abuse poured millions into research on MDMA. The results showed so little risk that MAPS used those findings when they successfully applied for research permissions and funds. Still, there’s a matter of public perception that’s not always productive.

“There is a tendency, especially with media organizations that rely on online advertising — i.e., clickbait — to over-exaggerate the results,” said Burge. “When you see that two-thirds of people with PTSD only needed two sessions of MDMA, they take that result and call it, “Ecstasy cures PTSD.’ It’s not just inaccurate; it’s irresponsible.”

Despite all the recent findings, he continued, “There are risks, and there is a lot of work involved in the therapy itself.” We have an opportunity now to be very clear.”

“A new paradigm” for psychedelics in mental health

While the positive effects of psychedelics on mental illnesses, particularly addiction, are observable, they are not necessarily explainable yet. However, thanks to advances in brain imaging technology, new theories may clarify what happens and why — and how to use those events therapeutically.

In the 2016 peer-reviewed study “Psychedelics as Medicines: An Emerging New Paradigm,” David Nichols, Matthew Johnson, and Charles Nichols argue that changes in behavior in a person using psychedelics are merely the “observable markers” of an underlying mechanism at work. They proposed a new hypothesis explaining this mechanism that’s consistent with existing data and test results.^[21]

Essentially, if addiction and other mental illnesses “rewire” the brain, psychedelics can help to restore the brain to how it was wired before the disease took hold. The restoration process, their paper says, would work “In much the same way that a computer can be rebooted when its operation becomes sluggish.”^[21]

Researchers have long understood the relationship between neurotransmitters and various mental disorders.^[19] As a result, pharmacological approaches to addressing mental illness were receptor-based. Most antidepressants, for instance, are Selective Serotonin Reuptake Inhibitors, or SSRIs. They work by making neurotransmitters like serotonin or norepinephrine more available to the brain.^[46]

Essentially, the authors say, SSRIs adjust the parts rather than fix the brain as a whole. By understanding how the brain is connected, and changing those connections, they can restore healthy overall functioning.^[21]

David Nichols, Adjunct Professor at the UNC at Chapel Hill Eshelman School of Pharmacy and Distinguished Professor Emeritus at the Purdue University College of Pharmacy, is one of the authors of “Psychedelics as Medicines.” He spoke with Third Wave about how the use of functional Magnetic Resonance Imaging, or fMRI, technology gives researchers a bigger picture of the brain at work.

It’s understood, Nichols said, that neurotransmitters signal each other from one area of the brain to the other. But, their precise pathways are mostly unknown.

Studies determine what areas of the brain are communicating by using a statistical analysis of brain activity. If one area generates a certain electrical pattern, and then another does the same, the analysis identifies the correlation, and researchers recognize it as communication or connectivity.

What’s new is that fMRIs revealed what researchers call “brain hubs.”  Each one is a complex region of the brain that appears segregated, almost walled-off, from the other regions. There’s a lot of communication and activity within each one, and then some connectivity and neuronal signaling to other areas.

This updated model casts neurotransmitters and pathways as merely components of a larger system, rather than independent systems themselves. Knowing this, researchers can think about fixing the machine as a whole, rather than just replacing a part here and there. Psychedelics may hold the key to doing so.

Factors such as mental illness can disrupt brain hubs, explained Nichols. They cause hubs to disconnect or stop working properly, weaken in places, or become stronger in others or talk to areas they’re not supposed to talk to.

Psychedelics affect connectivity in a different, potentially beneficial way. The psychedelic substances induce strong, long-range connections across the brain, creating a web of global functional connectivity.  They essentially knock down the walls of the hubs and allow the creation of many new connections across all the networks of the brain.

These new connections seem random; Nichols imagines neurotransmitters are following paths of least resistance within the brain rather than any set tracks. Then, the increased functional connectivity fades away as the substance wears off.

“The idea that these substances are mind-expanding really is literally true if you think about the way the brain communicates,” said Nichols.

With this information, he and others speculate that when psychedelics induce global connectivity, they also disrupt the unusual connections created by conditions such as addiction, anxiety, depression, and PTSD. When the effects wear off, the brain can reforge connections starting almost from scratch — without the forces that caused the previous hub connections. Using the substances in conjunction with psychotherapy would encourage the process.

For now, it’s only a hypothesis, but it may not be just that for long. If proven, however, it can represent a “new paradigm” in treating mental illness.^[21]

Nichols cites a study from the Imperial College of London that is nearly ready for publication. Correspondence with his colleagues revealed that the study demonstrates functional connectivity in people with those conditions returning to healthy patterns after psilocybin treatment.

“With functional connectivity, if we see [these results] with alcohol and nicotine, it will tell us these two brain areas are talking to each other in addicted brains, and they’re not supposed to,” he said. “That will foster more work in psychiatry and pharmacology. It will give us new insights into these pathological conditions.”

There are also two psilocybin trials treating people with nicotine and alcohol addictions at John Hopkins and New York University, respectively.

“We anticipate that it will show disturbed patterns in addicted brains compared with control brains. Presumably addicted or depressed brains show disturbances — connectivities that don’t exist in healthy brains,” Nichols said. “After psilocybin, you’ll see a loss in connections that are not supposed to be there.”

Conclusion and recommendations

Despite myriad information about the effects, risks, and benefits of opioids and psychedelics, it is still difficult to make long-range recommendations for how they should be regulated. However, we believe officials can take small, positive steps to promote the safe, legal, regulated use of both.

First, Third Wave recommends that psychedelics, or hallucinogens, such as LSD, MDMA psilocybin, ibogaine, etc. be removed from Schedule One classification. With fewer legal hurdles, researchers could more easily study their effects. In doing so, they can continue to find ways to use these substances in treating mental illnesses including addiction while assessing other benefits and risks.

As more information comes to light, further changes in regulating these substances can be made. Restricting their use to those over 18 or 21, such as with tobacco and alcohol, respectively, is one option. Instituting clinical guidelines, such as those outlined by MAPS, would facilitate research while reducing the risk of people using them irresponsibly in uncontrolled settings.

It is more challenging to call for the safe legal use of a substance such as heroin, with its many risks. However, there is also precedent for regulated use as a method of harm reduction.

One example is safe injections sites for users of intravenous substances such as heroin. Here, staff and medical personnel provide clean needles, teach safe injection practices, monitor users for signs of overdoses, and refer clients to substance use treatment and counseling if it’s requested. The idea is to decrease the public health burden of people with SUD while also containing the spread of diseases such as HPV.^[49]

The first safe injection sites opened in Vancouver, Canada in 2003, followed by a second in 2017. In 2016, the first site reported that 8,040 made 214,898 visits that year. The staff oversaw 1,781 overdose interventions and made 5,321 health and social service referrals.^[50]

Although still controversial, similar sites are being considered in Seattle, WA, and Philadelphia, PA.^[51][52][53] In January of 2018, Philadelphia city officials officially greenlit the establishment of safe injection sites in the city and began searching for partners and funders.^[53]

While the long-term effectiveness of safe injection sites remains to be seen, this is a positive step in the right direction of legal, regulated use. Similarly, while the paths to safe, regulated use of these substances are still open-ended, a first step is clear: removing the Schedule One classification will allow researchers to understand more about how psychedelics can be used safely for recreational, creative, and medicinal purposes.

About the Author: Jack Firneno is a Philadelphia-based dad, writer and drummer… but not always in that order. For more information, visit www.dadwriterdrummer.com.

Footnotes

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