Psychoactive compounds have been of interest to people for millennia. It is only recently, that some countries intensively started researching and potentially applying their positive effects. From ancient Amazon Forest tribes to modern Western world. Psychoactive compounds are slowly beginning to reach people around the world due to their unique effects. From widely used psychoactive compounds such as coffee, to exotic plants of the Amazon Rainforest. The variety and applicability are unprecedented.
We can find psychoactive compounds in many drugs, alcohol, plants, or even animal species. Most widely and commonly used psychoactive compounds are alcohol and caffeine. Most people consume them to change their mental state. They are both legal and easily available, however they can still be physically and psychologically harmful if consumed in larger quantities. Even though most of psychoactive compounds were taboo for a long time, nowadays many research institutions are granted funding for research in the field of their application. Furthermore, new findings on their positive effects are emerging very often and even health clinics that are treating patients with psychedelic compounds for various health issues are opening (example in Switzerland, Israel…).
In this article we will present the types of psychoactive compounds, their origins, and how they work. We will focus on psychoactive compounds derived from nature and will focus on segmentation of psychoactive compounds in cannabis in the end.
WHAT IS A PSYCHOACTIVE COMPOUND?
The term psychoactive compounds or “Psychedelics” was created by an English psychologist and researcher Humphry Osmond. It combines Greek words for mind or soul (psyche) and show (deloun), to describe the effect of LSD on the mind.
In principle, there are two ways to define if a substance is psychoactive. The first depends on the receptor binding, and the second depends on the comparison of the substance effects towards what we consider psychedelic effects. If a compound passes the test for either or both, then it is considered a psychedelic.
From receptors point of view, a compound is classified by scientists as psychoactive if it binds to serotonin 5-HT2A receptors (5-HT2AR) as an agonist or part-agonist (usually tryptamine compounds like serotonin). Hallucinogenic effect of agonist binding is mediated via 5-HT2AR signaling pathway connected to receptors. This pathway is still not well understood however, researchers theorize that in activates phospholipase C enzyme, which leads to release of inositol phosphates and diglycerol (signaling molecules). This causes the release of calcium ions from endoplasmic reticulum in the cell. The possibility, that other serotonin receptors are involved in the entire psychoactive experience is still not excluded.
TYPES OF PSYCHOACTIVE COMPOUNDS
Psychoactive or psychotropic compounds is a term used to describe substances that alter a person’s psychological state with affecting how the brain and nervous system work. This can lead to a “high” which is commonly the primary reason to use these compounds (but not the only one). They can affect our perception, mood, consciousness, and subconsciousness.
Most psychoactive compounds belong to one of the three chemical compound families:
- tryptamines (Psylocibin, DMT, tryptamine),
- phenethylamines (amphetamines, MDMA, methamphetamines),
- lysergamides (LSD).
All these substances bind to serotonin 5-HT2A receptors in our brain, which modulate the activities of sensory perception and cognition. We can also classify them by their effect on the body:
- stimulants (caffein, nicotine, amphetamine, cocaine),
- relaxants (alcohol, benzodiazepine),
- opioids (various painkillers such as codeine, morphine, heroin), and
- hallucinogens (psilocybin, LSD, ketamine, peyote)
It is hard to put cannabis only in one of the categories, as its effects (depending on cannabis type) can be very similar to other psychoactive compounds however, it works in a completely different way (binds to CB1 and CB2 receptors), via the endocannabinoid system. You can read more about the endocannabinoid system and how it works here. This makes cannabis a special type of plant, that brings various effects depending on the correct cannabinoid ratios. Below we will start by introducing the most popular natural active compounds, that cause a psychoactive effect.
Psylocibin is a hallucinogenic compound which can be found naturally in certain mushrooms in Europe, South America, Mexico, and USA. Mushrooms containing psylocibin are also called “magic” mushrooms. Psylocibin is usually used as a recreative substance, which can cause euphoria and affects our sensory perception.
The most general physical in psychological reactions is:
- feeling of relaxation (similar to low doses of THC rich cannabis),
- nervousness, paranoia, and panic reaction,
- introspective / spiritual experience.
Psylocibin activates serotonin receptors, most commonly in the pre-frontal cortex. The effect of psylocibin is usually felt after approximately 30 minutes of ingestion and can last for up to 4-6 hours. The effects strength is dependent on the type of fungi, origin, growth conditions, time of harvest, fresh or dried mushrooms (in dried mushrooms the amount of psylocibin can be up to 10x higher). More and more studies show that the right dosage of psylocibin can be an amazing cure for depression and other psychological conditions. It is also proven, that psylocibin does not cause addiction or compulsive use.
There is also an interesting theory of the “Stoned Ape”, developed by a psychoactive compounds research pioneer, Terence McKenna. The theory suggests that in ancient times, a large breakthrough in human thinking ability and enormous increase in cognitive ability happened due to magic mushrooms and their psylocibin. You can read more about the theory here.
LSD is one of the strongest psychoactive compounds. It is made of lysergic acid, which can be found in ergot fungi that grown on rye and other crops. It is usually made in illegal laboratories.
We can describe its effect as enhanced psychosis. Altered ability to recognize reality, rational thinking, and communicating with others. The users call the good experience “trips” and bad experience “bad trips”. In some trips, the users experience pleasant, mind stimulating experience that cause a feeling of increased understanding or even enlightenment. Bad trips can cause scary thoughts and feelings of anxiety and desperation, which can include fear of control loss, insanity, and death. The most general effects are:
- increased blood pressure, heart rate, and body temperature,
- dizziness, and sleepiness,
- loss of appetite, dry mouth, and sweating,
- numbness, weakness, and shivering,
- impulsiveness and sudden changes in emotion that can range from fear to euphoria with a change so sudden, that the user can feel multiple emotions at the same time.
DMT or dimethyltryptamine causes its effects through serotonin (5-HT) receptors in the brain, similar to LSD and psylocibin. Some research suggests that DMT can occur in our brain naturally in lower quantities. This leads to hypothesis that the release of endogenic DMT occurs when people report alien abductions, spontaneous disappearances, and near-death experience. However, this is still a very controversial topic.
The most general effects of consuming DMT are:
- increased heart rate,
- hallucinations, which often include a radical change of environment, as well as body and space distortions.
DMT is commonly used in various cultures for different rituals and ceremonies. Its effects are usually felt quickly, are intense, and do not last very long. The effects can last for 3 hours or more, if DMT is ingested orally together with MAOI (monoamine oxidase inhibitors). An example of this combination is ayahuasca tea, that many amazon tribes are practicing. DMT can cause very real hallucinations or projections of mystical experiences, that include feelings of euphoria and dynamic, geometric shape hallucinations. DMT can be found in various plants such as Anandenathera peregrina, Anandenathera colubrina, and many others. In the video below you can watch an ayahuasca experience in which experts from psychedelic fields are included.
Tetrahydrocannabinol (THC) is the main psychoactive compound in cannabis and one of over 144 cannabinoids present in cannabis. The term THC is usually connected to Delta-9-THC. It is believed THC occurred in cannabis due to plants evolutionary adaptation, mostly against insect predators, UV light, and environmental stress. We will discuss THC later in this article.
For the conclusion of this part, we would also like to mention two additional psychoactive substances called Peyote and psychoactive frogs.
Peyote is a small cactus with a main hallucinogenic psychoactive compound called mescalin. It has been used by native inhabitants of Mexico and SW USA since ancient times, as a part of traditional religious ceremonies and for its healing abilities. Mescalin can be an extract from peyote or also synthetically produced in a laboratory. The most general effects on the body are:
- increased body temperature and heart rate,
- uncoordinated movement (ataxia),
- heavy sweating,
- alternative states of perception and feelings.
This relatively newly popular compound is a venom of a toad, which lives mostly in Sonoran Desert (Arizona, California). The Colorado river toad or Bufo Alvarius is a rare toad type, that releases 5-MeO-DMT venom. It is a very strong natural psychedelic, 4-6 times stronger than DMT. People used to lick toads to experience this effect, however nowadays their venom is extracted, dehydrated, and consumed in powder form. Shamans in Mexico and SW USA have been consuming this substance for a very long time.
The effects occur already after 5 minutes from consumption. It can cause a very strong spiritual journey which lasts approximately 1 hour. After the experience, individuals claim to feel reborn, one with the universe, and that they felt merged or connected with “god” during the experience.
Many psychoactive compounds can lead a person to a point of complete ego dissolvement. A person can experience extraordinary transformation of how they view the world, connectedness, and thinking. In this process our brain works similar to resetting a computer and starting with a fresh desktop.
However, it is important to note that for some people, using psychoactive compounds can be very dangerous and is not recommended without supervision or advise from a professional. The mentioned experiences were acquired in a controlled, safe environment for research purposes.
PSYCHOACTIVE COMPOUNDS IN CANNABIS
In cannabis we can find more than 144 different cannabinoids. The most known cannabinoids are cannabidiol (CBD) and tetrahydrocannabinol (THC). THC is the main psychoactive compound in cannabis. THC’s chemical formula describes different isomers however, the term THC is usually connected to isomer Delta-9-THC.
THC was discovered and isolated by chemist Raphael Mechoulam in Israel in 1964. With his team they discovered that THC is absorbed into bloodstream when smoked, and travels to the brain where it binds to the natural endocannabinoid receptors. In the video below you can watch the documentary connected to Dr. Mechoulam and the discovery of THC and cannabinoid science.
Different cannabis species have different amounts and ratios of THC and CBD. Usually, industrial cannabis has very low levels of THC and higher quantities of CBD. On the contrary, medical cannabis has very high THC levels, and CBD levels can be high as well (if this kind of ratio is demanded).
CBD and THC
CBD and THC both have the same molecular structure. It contains 21 carbon atoms, 30 hydrogen atoms, and 2 oxygen atoms. Their completely different effects after consumption are affected by the slight change of atom allocation. They are both very similar to our bodies endogenic cannabinoids (endocannabinoids), which allows them to interact with the receptors. This interaction affects the release of neurotransmitters in our brain. Neurotransmitters are responsible for transporting information between cells and have a great role in regulating pain, immune function, stress, sleep and many other.
Although their chemical structure is similar, they do not have the same psychoactive effects. Technically, CBD is psychoactive but does not cause the “high” connected to THC. CBD proved to be a great asset in mitigating anxiety, depression, and various seizures.
On the other hand, THC binds to CB1 receptors in our brain and can cause the “high”. CBD binds very weakly to CB1 receptors or does not bind at all. If it wants to bind to these receptors, it requires THC and in combination also reduces euphoric and other psychoactive effects of THC. Both cannabinoids can have many positive effects for various health conditions. In some they are more effective together, and in others individually.
CBD is used to help with many different conditions including:
- psychosis and mental disorders,
- bowel inflammation,
- sleep disorders.
While THC can help with conditions including:
- muscle spasm,
- sleep disorders,
- loss of appetite.
While CBD does not have side effects, THC can cause the following short-term side effects, depending on dosage:
- increased heart rate,
- coordination problems,
- dry mouth,
- red eyes,
- longer reaction time,
- loss of short-term memory.
It is also important to emphasize that none of the mentioned cannabinoids can cause death (even in high dosages). However, very frequent use of THC, especially with minors, can result in long-term psychological consequences. This is an assumption, although there are no final conclusions that THC can actually cause psychological conditions such as schizophrenia.
Currently, most of the European countries have a THC product limit of 0,2% (Slovenia as well) or 0,3%, and up to 1%. Such low percentages of THC usually do not cause psychoactive effects, that are often discussed. However, these rates are highly important to achieve the “entourage effect” of cannabis. You can read more about it here. Products that include THC among other cannabinoids are also called FULL SPECTRUM products.
Effects on the Body
THC stimulates brain cells to release dopamine and consequently cause a euphoric felling. It is also involved in hippocampus information processing, which is the part of the brain responsible for new memories. THC can trigger alternative thinking and delusions, even hallucinations. On average, the effects last around 2 hours and start from 10 to 30 minutes after consumption. Psycho-motor disturbances can last for some time after the end of “high” feeling.
DELTA 9 THC and DELTA 8 THC
Delta-9-THC is the primary component of cannabis, which causes psychoactive effects and is abundant in cannabis. Similar to Delta-8-THC, both bind to the endocannabinoid system of our body. Chemical similarity is also in the double bond they both have in their structure. It is assumed that this double bond creates the intoxicating effect that causes the “high”. Chemically, they differ in the location of the double bond. They both have a chain of carbon atoms; however, Delta 8 has a double bond on the eight-carbon atom and Delta 9 on the ninth carbon atom. Due to this difference, they interact with the endocannabinoid system a bit differently, which most probably causes the weaker effects of Delta-8-THC.
Because Delta-9-THC is very abundant in cannabis, its direct extraction is relatively simple and cost effective. It is mainly extracted from THC rich cannabis (and not from industrial cannabis). On the other hand, we have Delta-8-THC extraction, which requires a bit more effort as it occurs as a minor cannabinoid in cannabis. Because cannabis produces very little Delta-8-THC it is too difficult and too costly to directly extract it from the plant. There is however another way of producing Delta-8-THC. It was discovered that it can be completely synthesized from CBD using solvents. Although the process is a bit pricier, it has greatly eased the production of this isomer. In this way most of the Delta-8-THC is extracted from industrial or CBD rich cannabis.
Furthermore, due to this ability, Delta-8-THC is increasingly used to exploit the loophole in the legislation of some countries, that allowed farmers to grow industrial hemp. Delta-8-THC which can be produced from these plants is not mentioned anywhere in the legislation. This is still a very grey area that is on the rise in some countries such as USA.
The Difference in Effects
One of the greatest differences between Delta-9-THC and Delta-8-THC are the effects that they cause. Delta 9 has a stronger effect compared to Delta 8. Some people claim it is 2x stronger and consequently also causes more side effects (mentioned above in this article). On contrary, the consumers report that Delta 8 causes an easier, light experience. Most people experience the feeling of calmness and clarity. Many people experience the “high”, but not enough to affect their ability to think clearly and focus on the activity in progress. Simply put, they feel more relaxed and less stressed. Both THCs are also different in the time it takes for the effects to kick in. Delta 8 works slowly and gradually takes a person to the relaxed state. On the other hand, Delta 9 works faster and instantly.
A LOT OF RESEARCH AND TESTING TO BE DONE
Psychoactive compounds are present in the human culture for millennia. From religious ceremonies, to visions, healing, and changing people’s way of thinking and perspective, they absolutely affected how humans developed in a great way. Demonizing, completely forbidding, and the lack of scientific discussion in this area seems very unjustified. Many have proven that they can help with many psychological barriers and improve health conditions at the correct dosages. However, we have to be careful as people have different tolerance, life experience, psychological conditions, life phases that can greatly affect the experience. In this way one psychoactive compound can affect one person positively and the other person negatively. Much research will have to be done nevertheless, to discover at least an approximation of the absolute truth.
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G. D. C.
19. 10. 2021