A Scientific Explanation of the Psychedelic Experience
This article is my attempt at providing the most scientifically accurate and factually legitimate explanation of the psychedelic experience as I possibly can. It is a complete overhaul of my previous sensory filter article and I have done my best to provide citations with the correct formatting to supporting studies every step of the way.
My understanding of this topic has recently increased greatly since I have started deliberately reading up on neuroscience in general, so I will try my hardest to supply as much solid evidence for as I possibly can. But if you know more about these things than I do and want to contribute ideas of your own or debate mine please do so. Any help with this would be great as my knowledge of neuroscience barely extends beyond what Wikipedia has managed to teach me over the past few months.
I have to admit though, this article relies on both scientific studies and my personal experience with psychedelics. Which I personally cannot prove to people unless they have tried the substances themselves.
Regardless, please point out flaws in my logic, evidence and grammar as I am sure there are plenty of them. In return I will continuously update this article until it becomes as accurate as I can possibly make it.
How drugs work – Antagonists vs Agonists:
In pharmacology there are two basic categories that all drugs fall under. These two possible types of substance are known as either agonists or antagonists.
There are of course subgroups to these two main categories, but for the sake of keeping this article as simple as possible I am only going to give a basic rundown.
Put simply, an agonist is a chemical that binds to a receptor and produces a biological effect. These compounds usually mimic the structure of an endogenous neurotransmitter and fit into its same receptors. Their neurophysiological effect on behavior can be either stimulatory or inhibitory, depending on the function of the neurotransmitter that they mimic. For examples amphetamines are neurophysiologically excitatory because they structurally mimic dopamine which is a neurotransmittor that stimulates behavior.
In contrast however, GABA-ergic neurons are inhibitory, so GABA agonists such as benzodiazepines usually inhibit neural activity and behavior causing muscle relaxant and sedative-like effects.
On the opposite end of this spectrum, an antagonist is a molecule that binds to a receptor but does not produce a biological effect. These compounds are inactive so instead block or inhibit the actions of specific neurotransmitters and agonists. For example, NMDA receptor antagonists (such as ketamine) block the receptor that allows for the transfer of electrical signals between neurons in the brain, and in the spinal column creating for its dissociating and anesthetic-like effects. On the other hand, since GABA-ergic systems across the brain are inhibitory, GABA antagonists therefore usually stimulate behavior.
Psychedelics – their chemistry and receptor target sites:
In this article, the use of the term “psychedelic” will be in reference to three structural groups:
- chemicals that are chemically and pharmacologically similar to psilocin and DMT.
(the tryptamine hallucinogens)
- chemicals that are chemically and pharmacologically similar to LSD and LSA.
(the lysergamide hallucinogens).
- chemicals that are chemically and pharmacologically similar to Mescaline, DOI and the 2C family.
(the phenethylamine hallucinogens)
These three groups of chemicals have shared pharmacological targets and produce extremely similar behavioral effects (discussed later). Hence, it makes sense to group them together. The three groups of drugs are known in the literature as the serotonergic psychedelics, as they are all characterized with a method of action strongly tied to the serotonin neurotransmitter. Serotonin (often referred to as 5-HT, short for its full chemical name 5-hydroxytryptamine) is a naturally occurring neurotransmitter which is tied to appetite, sleep, memory, learning, mood, behavior, depression, positive mood, certain involuntary muscle control, and countless other functions, many of which are not yet fully understood.
This puts psychedelics in a class known as Serotonin receptor agonists, because they excite our 5-HT receptors. More specifically, they hold a particular affinity with a subset of our 5-HT receptors known as the 5-HT2a receptors. It’s 5-HT that the classic psychedelics have been shown to mimic, to the point where the structural similarities between these three groups to serotonin can be seen at a mere passing glance as the comparison image below demonstrates.
It is likely that the 5-HT2a receptor is the primary site of action for psychedelics for many reasons and this claim is backed up by a large body of evidence. The first evidence that psychedelics act via the 5-HT2 receptor was published in the paper by Glennon et al., (1983). This paper, using a drug discrimination task, trained rats to discriminate between the phenethylamine psychedelic DOM and a placebo in a two-lever operant choice task. Successfully demonstrating that when rats were administered doses of mescaline, LSD and 5-MeO-DMT, they still chose the DOM stimulus lever. This heavily suggests that the effects of DOM can be generalized to both indole and other phenethylamine hallucinogens, but not other 5-HT receptor agonists which the rats were also exposed to. It was also shown in the same study that this stimulus generalization was consistently blocked by the 5-HT2 receptor antagonist, ketanserin, showing that these three psychedelic compounds must involve those sub-populations of serotonin receptors that are blocked by ketanserin (i.e. 5-HT2 sites).
Glennon et al., (1984) then reported that the affinity of various hallucinogens for 5-HT2 subtypes, but not for other receptors, was tightly correlated with the drugs’ ED50 in human usage and rat drug discrimination experiments.
ED50 is a pharmacological term that simply means the dosage at which a drug begins to show effects in 50% of the population using it. This is a correlation that has been shown multiple times (Sanders-Bush et al., 1988) alongside a large number of agonist/antagonist experiments (reviewed by Nichols, 2004) and it is due to this consistent evidence that the scientific consensus has generally agreed on 5-HT2 receptor subtypes as the primary site of action of psychedelics.
Now that we know which receptors are responsible for the psychedelic experience, it makes sense that to understand how psychedelics affect consciousness we must first assess the location of these 5-HT2 receptors. This is something that has been studied using what is known as immunocytochemistry to localize 5-HT2a receptors in tissue samples. Immunocytochemistry or IHC is the process of staining antigens (e.g., proteins) in cells of a tissue section, by exploiting the principle of antibodies binding specifically to antigens in biological tissues and attaching them to a marker such as a fluorescent dye. Jakab and Goldman-Rakic (1998) examined macaque brains using this technique and found dense 5-HT2A receptors throughout all cortical regions, specifically in areas heavily involved in consciousness and sensory processing or more specifically the frontal, prefrontal, temporal and occipital cortices.
Besides these, it has also been shown that 5-HT2a receptors are contained within multiple parts of the thalamus which is an area at the top of the brain stem with functions that include relaying sensory and motor signals to the cerebral cortex, along with the regulation of consciousness, sleep, and alertness. Pompeiano et al., 1994 used yet another method of tissue staining known as in situ hybridization to show that the reticular, lateral geniculate nuclei of the thalamus all contain 5-HT2a receptor mRNA. These two areas are both involved in the relaying of information from sensory organs to their appropriate cortex and have been heavily speculated to play a large role in the psychedelic experience (Lambe & Aghajanian, 2001; Marek et al., 2001).
Now that the general distribution of 5-HT2a receptors has been established, we can begin to infer how psychedelics affect consciousness in greater detail by assessing the function of these neurological components and how they react when exposed to serotonergic psychedelics, as shown by various scientific studies.
The effects of psychedelics on different regions of the brain and how this translates into the psychedelic experience:
One of the most important areas of the brain that psychedelics have an affect on via means of 5-HT2a excitation are on the pyramidal neurons of the brain.
Pyramidal neurons are a type of neuron that are distributed all across the brain in the cerebral cortex. The cerebral cortex is a sheet of outer neural tissue that surrounds roughly two thirds of our entire brain mass. It is the most highly developed part of the human brain and is responsible for sensing and interpreting input and maintaining cognitive function via the four basic lobes that comprise it. These lobes are:
- the Temporal lobes - involved with auditory perception, and language processing.
- the Occipital lobe - involved with vision.
- the Parietal lobe - involved in the reception and processing of sensory information from the body.
- the Frontal lobe - involved with consciousness, decision-making, problem solving, and planning.
This cerebral cortex is divided into 6 different cortical layers, each of which contain a characteristic distribution of neuronal cell types and connections with other cortical and subcortical regions. It is at layer five however where the densest collection of pyramidal cells are found.
The medial prefrontal cortex (mPFC) is a part of the frontal lobe that is specifically in charge of complex cognitive behavior, personality expression, decision making and the orchestration of thoughts and actions in accordance with internal goals. 5-HT2a receptor activation of the prefrontal cortex’s pyramidal cells has been shown by multiple studies to cause sharp increases in the amplitude and especially frequency of spontaneous excitatory postsynaptic currents (EPSCs) from within these cells (Aghajanian & Marek, 1997; Aghajanian & Marek, 1999; Marek & Aghajanian, 1999; Marek & Aghajanian, 1998).
The cells that were most excited within the mPFC were layer five pyramidal neurons. Areas where applying 5-HT to the cortical slices produced the most robust EPSPs when recording from layer five pyramidal cells, closely matches the distribution of 5-HT2A receptor, i.e. layer one and especially layer 5a Goldman-Rakic & Aghajanian, (2000).
As reviewed above, the mPFC cells that seem to be excited most by application of 5-HT2a receptor agonists are layer five pyramidal neurons. Layer five pyramidal neurons across the brain have diverse intracortical projections and importantly, project to many non-specific thalamic nuclei. They are unique in the fact that they mediate multiple pathways of sensory processing and perceptual feedback analysis, and in a theory reviewed by Jones (2002) have been implicated in the binding of separate sensory stimuli into a discrete conscious event.
By activating layer five pyramidal cells’ coritco-cortical and corticalthalamic projections, psychedelics cause the spread of high-frequency oscillations to areas that would not normally be activated. Agonism, disinhibition and excitation in layer five recurrent circuits would therefore necessarily lead to multisensory frame aliasing errors, feedback synesthesia, and eventual perceptual/ sensory overload. This provides a neurological basis for an explanation to two out of the four different categories of sensory effects that are found in varying levels of intensity and style across all of the classical psychedelics.
The first of these two separate sensory effects manifests itself in multiple ways but is recognizable as what the psychedelic community has named as “visuals”. Visuals can be described as the sensation of a person’s field of open and closed eye vision being partially or completely encompassed by fast-moving kaleidoscopic and indescribably complex geometric patterns, form constants, shapes, fractals, structures and colour. Common descriptions of visuals are generally along the lines of the geometry being fractal representations of repeating forms, embedded within each other. This geometry commonly includes vast and intricate form constants that among many other things, take the style of webs, grids, checkerboards, spirals and funnels in a huge variety of colours.
These visuals never stand still at any point and are extremely fast changing in terms of their shape and style within themselves. This happens whilst they are naturally drifting laterally or radially across the visual field to create overlapping webs of many arising and decaying geometric patterns, all of which are visible within a single perceptual frame.
When experienced, visuals somehow have a deep sense of profoundness and importance attributed to them, and feel as if they are perfectly fitting geometric representations of your current mind state. For simple examples of this, visuals consistently fit a person’s mood, becoming bright, colourful and somehow happy in appearance when a person is in a positive state and becoming dark and ominous if a person is in a negative state.
It’s because of this, among other things, that I have been led to believe that visuals are the experience of the brain’s pyramidal neurons becoming agonised and therefore erratic and excitable sending off information they normally wouldn’t. This leads to the electric signal in these neurons to “bleed” and soak into other pyramidal neurons including neurons that are directly adjacent to them and elsewhere across the cerebral cortex. This creates several different effects but most notably causes information from pyramidal neurons within the prefrontal cortex and from other sensory cortices to leak into visually connected pyramidal cells within the occipital lobe. The visual cortex then attempts to interpret this as visual information creating random noise which higher brain functions attempt to constrain meaning upon. This idea essentially means that visuals are the literal exposure of a person’s conscious faculties to the brains subconscious neurological structure. This is something that is backed up by not just the way psychedelics have been shown to affect the brain through scientific study, but by the analysis of the behavior of it’s subjective experience.
Visuals start at lower levels of tripping, as geometric patterns that increase in intensity, eventually begin encompassing and overwhelming your entire visual field. As the amount of neurological structure that is experienced increases proportionally with dosage, the amount of information from across the cerebral cortex that a person is exposed to eventually increases to something near 100%, leading to a person being exposed to the organization of the entirety of their mind at once. This is consistently described as feeling as if you are experiencing everything in the universe simultaneously in a single instant. It is described as profound and infinite in size. As this is happening, the vast data stream of neurological structure and geometry that is experienced begin to destroy the ego through complete sensory and perceptual overload, which is exactly why the psychedelic community has come to call this state ego-death.
This results in an altered state in which you are conscious, but your short term memory has been destroyed, making you completely incapable of maintaining functional, linear thought. Since this sensory overload increases proportionally with dosage it can be thought of as a set of scales. As visuals go up, the ego goes down, and vice-versa. Due to this, once the level of neurological exposure hits 100% and a person starts to feel one with the universe, the ego becomes proportionally eradicated due to the brain’s pyramidal neurons no longer being able to process data efficiently, because of the extreme excitation and perceptual overload. This gives rise to the highest possible level of psychedelic experience.
It’s also worth mentioning that visuals increase in intricacy and intensity relative to the amount of a persons current sensory input, something that one would expect if visuals are the result of neurological / sensory information being rooted through our visual cortex.
For example, adrenaline and physical exertion seem to cause a proportional increase in visual intensity across all people. More personally, I have unintentionally triggered spontaneous ego-death well after the peak of a trip simply by leaving my quiet bedroom and stepping outside into the harsh winds and rain of British winter on more than one occasion. I would hypothesize that such things are the result of increased sensory input leading to a higher amount of information being available for routing through the visual cortex and therefore leading to greater amounts of perceptual and sensory overload.
However, if any of this is true on a neurological level, It would simply make sense that this would be experienced in other forms through different senses, as there is no reason that erratic and excitable pyramidal neurons would favor sending irrelevant information to visually connected cells over any other area within the brain.
In my opinion, although in a form that is not nearly as complex and earth shattering as visuals to experience, these definitely exist and are quite common, but not as universal an experience. The two other commonly reported sensory equivalents that seem to stem from the same mechanism are what I and others refer to as “audio effects” and “body high” or “body load”.
Audio effects are a distinct category of and completely separate from audio hallucinations which I will go into later. They can generally be described as hearing noises such as; reverb, tones, and general sound effects, that often seem to follow and fit thought patterns and processes. Common examples of these include pitches and notes that increase in intensity the harder you concentrate or hearing the sounds of an all consuming tone during the initial come up of DMT. They can also be experienced in the form of sounds such as soft purring or multiple tones and phasers, but they are essentially limitless in their possibilities in and completely rhythm-less in tune. I find these sorts of audio effects to be extremely common on DMT and have seen multiple people under the influence of Ayahuasca comment on the fact that they can hear a gentle humming of white noise in the background, as if you can hear the very mechanics of your brain at work.
It’s through my personal experience and reasoning, along with scientific data, which has made me come to the conclusion that audio effects are essentially the heard equivalent of visuals, working through the exact same mechanism as visuals, but with the neurological structure pouring over into a person’s temporal lobe and audio cortex, as opposed to their visual cortex.
The final lobe of the cerebral cortex which I have yet to relate to the psychedelic experience is the paretial lobe. This lobe is in charge of touch and the processing of sensory information from the body and is undoubtedly exposed to erratic electrical signals and information from pyramidal neurons just as our audio and visual cortex are. This is what I think results in the distinct and often overwhelming physical sensations found on the peak of a psychedelic trip that people generally refer to as a body high, which can be described as euphoric tingling sensations and random sensory noise felt through every nerve ending across the entire body.
Hopefully, I have adequately made my case above that these three distinct and separate sensory effects stem from the same mechanism and can therefore be categorized under that same mechanism accordingly. I am now going to go into how this very same pyramidal neuron excitation results in a completely different class of hallucination through an extremely similar but alternative mechanism.
The second visual effect that I am going to explain is what the psychedelic community refers to as distortions. This category of sensory effect is a very common one and behaves in a completely different fashion to visuals. Instead of fast moving geometric shapes that seem to appear from nowhere, distortions are open eye alterations and changes in perception attributed to the external environment. They are always obviously grounded in reality and begin at lower doses as a wiggling or drifting of straight edges and depth in the visual field. At higher doses they become impossible to ignore with the lines, textures and color between solid objects appearing to bend, swirl, or melt into one another. Often until the original object becomes completely unrecognizable. They are most commonly manifested as objects and scenery in your visual field, acting as if they are morphing, melting, bending, changing colour, vibrating and wiggling. Moving objects will have distinct and colourful tracers left behind them, while textures will also appear to physically creep across themselves; an effect which is most commonly seen on carpets and wood grain. Depth perception will become distorted in such a way that objects in the background may move into the foreground and vice versa, or depth perception can be lost entirely as a persons entire visual field flattens into a single unified image. Every visual distortion builds up and increases in intensity when stared at, but immediately resets to its original state once you double take.
Just as you would expect, distortions are not limited to a single sense but can be found with both a visual and an auditory equivalent. Audio distortions are not a universal experience but can happen spontaneously on any psychedelic. They are more common on some than others however, being particularly common on the 2C* phenethylamine family, mescaline and high doses of harmine. At lower doses they can be described as the experience of an echo or murmur rising in the wake of each sound. These increase proportionally with dosage up until the fairly simple experience of music having continuous reverb and sounds beginning to bounce across your brain as they replay continuously.
A combination of observing the behavior of visual and auditory distortions and looking at the neurological evidence has led me to the conclusion that they are generated by the same pyramidal neuron excitation as visuals. As pyramidal neurons are excited and begin to erratically send out information, it makes sense that at lower dosages, before pyramidal neurons gain the signal strength to fire information across to the other parts of the brain across the cerebral cortex, that they would only have the strength to send information to adjacent and nearby similarly excitable pyramidal neurons. This would create a system of cycled information as signals leak from their original source into nearby cells are then “fired off” again back into the original source of the signal, which due to it’s excitability would proceed to send out the same information once again, causing a continuous loop. Each time the original signal is reprocessed on top of itself, the original signal would become more degraded than before. This creates for sensory inaccuracies that continuously build up onto themselves through a system of recursive looping.
This explains why distortions increase when stared at, but reset when looked away from. It’s because still and out of focus eyes allow the loop to continue undisturbed, but new input immediately breaks it. It also provides an explanation for distortions happening at lower doses to visuals, as the mechanism behind it only requires pyramidal neurons to be capable of reaching the adjacent cells around them and no further. The fractal effects found within visuals however are closely related to this recursive visual looping.
For those who don’t know, fractals are patterns that repeat into themselves allowing for the same self similar image to be found no matter how far you zoom into any part of the image. They are an extremely common component embedded within the geometric patterns of closed eye visuals. Within mathematics, fractals are generated through recursive formulas that infinitely repeat an image over itself in a self similar way. Therefore, it would make sense that the fractals you see within the visuals are extremely similar self repeating recursive systems. These fractals are created because your brain’s recursive looping system is reinterpreting the same stimuli multiple times, causing the geometry to flower out into the fractals that the psychedelic community is extremely familiar with.
The third sensory effect that I am going to explain the neurological basis behind and the subjective experience of, is perhaps the most profound subjective sensory effect that the psychedelic experience has to offer. This sensory effect is known as a hallucinatory state, beginning at lower doses as imagery embedded within the visuals which can be described as spontaneous moving or still scenes, objects, people, animals, flowers, places or anything you could possibly imagine. They are often formed out of visuals themselves and are displayed in varying levels of detail ranging from “cartoonish” in nature to completely realistic, rarely holding form for more than a few seconds before fading or shifting into another image.
On certain psychedelics, such as LSA, ayahuasca and harmine, the imagery is manifested as an exact visual representation of whatever you are currently thinking about in your minds eye, turning abstract ideas into a concrete image. This particular manifestation of imagery only happens on psychedelics that allow you to slip into different variations of an extremely similar trance-like state; a state that is simply not found within any of the stimulating psychedelics.
As these states of imagery become increasingly elaborate (proportional to dosage), they eventually become all encompassing fully-fledged 3D hallucinations. These could be anything but generally fall under common archetypes such as induced mystical states, contact with autonomous entities, imagined landscapes, spirit dimensions and situations that seem so unlike anything previously experienced that they are in all probability untranslatable into English. Hallucinations often feel extremely mystical, spiritual and religious in nature regardless of the trippers theistic beliefs and it’s not uncommon for people to report that high level psychedelic hallucinations feel infinitely “realer” than anything the person has previously experienced.
For multiple reasons, it seems to me that these hallucinations are caused when high dose psychedelics trigger dreaming in fully conscious trippers. My reasoning for this is based not just on the behaviour of the experience itself but various studies which support similar conclusions. First of all, it’s definitely worth noting that psychedelic hallucinations look and feel exactly like extremely vivid dreams. The feelings of amnesia commonly felt after strong DMT trips are identical to that of the extremely familiar feeling of not being able to remember a vivid dream immediately after you have woken up. In fact, it is not uncommon for people to recognize places from within past dreams during states of psychedelic hallucination.
My second line of reasoning to support this is that the imagery seen within closed eye visuals (the state before hallucinations) feel exactly like triggered states of hypnagogia.
Hypnagogia is the state before fully-fledged dreams when a person is between being awake and falling asleep. It’s here where many people experience mild hallucinations, imagery and a fluid association of ideas. In fact, hypnagogia is thought to be characterized and based on a mental function, known as “auto-symbolism”, which are a person’s thoughts and ideas being made to manifest in their minds eye, identical in sensation to states found on multiple psychedelics.
Hallucinatory states however can be shown to be states of triggered conscious dreaming through more than just casual observation. This is because it has been demonstrated through neurological studies that psychedelics activate parts of the brain heavily associated with dreams and schizophrenia, besides creating the visual and perceptual alterations described above. Activation of 5-HT2a and 5-HT1a receptors in the medial PFC (mPFC) has been shown to have downstream effects on dopaminergic activity through descending projections to the ventral tegmental area (VTA) (Bortolozzi, A. 2005). This means that through increasing the firing rate of dopamine neurons in the VTA, dopamine release is triggered (Roser Cortés, and Francesc Artigas. 2009).
The VTA is in charge of dopamine release throughout the brain which is a neurotransmitter associated with pleasure seeking and motivation. It is also associated with symptoms of schizophrenic delusions when dopamine it is over produced within the brain. In fact, the most effective medications for treating patients with schizophrenia are those that prevent dopamine from binding to dopamine receptors. It’s also worth noting that amphetamine, cocaine and similar drugs which all directly increase levels of dopamine in the brain can cause symptoms which include bizarre and vivid dreams and those present in psychosis, particularly after large doses or prolonged use. This is often referred to as “amphetamine psychosis” or “cocaine psychosis,” but may produce experiences virtually indistinguishable from the positive symptoms associated with schizophrenia.
This is important because studies have shown that dopamine is the very neurotransmitter that triggers not only psychosis, but dreaming as well (Gottesmann C. (2002), Mark Solms. (2000)) , which provides an excellent and extremely likely neurological basis for the hallucinations and delusions experienced during a psychedelic trip grounded in states of triggered dreaming.
The fourth and final sensory effect that I am going to explain on both a subjective and neurological level is the complete loss of sensory filtering that occurs across all psychedelic compounds on extremely low doses. A loss of sensory filtering is the first sensory alteration that occurs with psychedelics and is noticeable at what could be referred to as threshold doses. These low level effects can be described as an increased bodily awareness alongside a complete enhancement of the senses most notable for our sight, sound and touch.
For visual perception specifically this can be described as the experienced of brightened colors, sharper edges and the ability to comprehend your entire visual field, including your peripheral vision. A common example of this is the sensation of staring at complex scene such as a tree and comprehending the exact position of all of its branches in your visual field all at once, instead of just the simple few that are in focus.
For audio perception this can be described as a heightened awareness of sound in general. An extremely similar ability to comprehend every layer of complex sounds, and the precise position and direction from which they are coming from in your surroundings is also present. A common example of this is the greatly enhanced music appreciation that stems directly from this effect.
For tactile perception this can be described as an enhancement of physical sensation whilst being able to feel and comprehend every nerve ending across the entire surface of your skin. On certain psychedelics, particularly LSD, this is accompanied by greatly increased bodily awareness and control, resulting in the ability to trigger movement in muscles across your body with a sense of control simply not found during sober living.
A loss in the brain’s ability to effectively filter out irrelevant sensory input resulting in an enhancement of the senses during a psychedelic experience is backed up by numerous neurological findings. Many large scale theories of psychedelic action involve their effects on the thalamic reticular nucleus (TRN). The TRN is seen to work as a filter for transmission of information from the thalamus to the cortex (reviewed by Guillery & Harting, 2003). It essentially regulates the filtering of incoming stimuli to discriminate from irrelevant background stimuli and is the physical location of the brains sensory filter. TRN neurons are nearly exclusively GABA-ergic, meaning that they are self inhibitory. It’s because of this that in a model proposed by Vollenweider and Geyer (2001) activation of 5-HT2a receptors on TRN neurons could activate them in the same way that 5-HT2a receptors activate GABA-ergic neurons in the cortex, and hence decrease the ability of the TRN to gate information flow effectively, resulting in a complete loss of sensory filtering and a loss of focus as the conscious faculties are exposed to a huge data stream of “irrelevant” information.
Now that I’ve covered all four groups of sensory effects that are universally experienced during a psychedelic trip, I am going to explain the neurological basis behind one of the most common and interesting mental effects of the psychedelic experience.
This effect is the deep and overwhelming sense of appreciation, profundity and importance attributed to a persons external environment that is felt during a psychedelic experience. It commonly makes every day objects seem absolutely fascinating and nature seem overpoweringly beautiful and deeply important.
The basis for this mental component of the psychedelic experience can be found in the locus coeruleus. The locus coeruleus (LC) has been reffered to as the “novelty centre” (Sara, S. J. 1995). It uses the neurotransmittor known as noradrenaline to focus your attention on something important, such as an attack, before the sensory information reaches your cortex. It has been shown that psychedelics posses an ability to alter the firing of the locus coeruleus (LC) and greatly increase the amount of noradrenaline it produces (Rita J Valentino. 1996). Systemic administration of either phenethylamine or indole hallucinogens to anaesthetized animals causes a 5-HT2a receptor dependent decrease in the spontaneous activity of the LC, but an increase in activity evoked by sensory stimulation (Aghajanian, 1980; Rasmussen & Aghajanian, 1986; Rasmussen et al., 1986).
It seems highly likely then that the increase in sensory evoked LC firing could produce some of cognitive effects induced by hallucinogens, such as extremely attentive states and ordinary objects appearing fascinating.
Large sections of this may be based on personal experience, but I’d like to think that based on my extremely basic understanding of how the human brain works this does seem to be how the sensory components of a psychedelic experience are generated and I challenge you to debate me at any point.
To further express my ideas on how this works simply I have created the chart below. The concepts on it show what I’m trying to express and each part depends on the component to its left and leads on to the components to its immediate right. You’re going to have to click to enlarge I’m afraid.
GLENNON, R.A., YOUNG, R. & ROSECRANS, J.A. (1983). Antagonism of the effects of the hallucinogen DOM and the purported 5-HT agonist quipazine by 5-HT2 antagonists. Eur J Pharmacol, 91, 189-96. http://www.ncbi.nlm.nih.gov/pubmed/6617740
GLENNON, R.A., TITELER, M. & MCKENNEY, J.D. (1984a). Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sci, 35, 2505-11. http://www.ncbi.nlm.nih.gov/pubmed/6513725
SANDERS-BUSH, E., BURRIS, K.D. & KNOTH, K. (1988). Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis. J Pharmacol Exp Ther, 246, 924-8. http://www.ncbi.nlm.nih.gov/pubmed/2843634
NICHOLS, D.E. (2004). Hallucinogens. Pharmacol Ther, 101, 131-81. http://www.ncbi.nlm.nih.gov/pubmed/14761703
JAKAB, R.L. & GOLDMAN-RAKIC, P.S. (1998). 5-Hydroxytryptamine2A serotonin receptors in the primate cerebral cortex: possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites. Proc Natl Acad Sci U S A, 95, 735-40. http://www.pnas.org/content/95/2/735.abstract
POMPEIANO, M., PALACIOS, J.M. & MENGOD, G. (1994). Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. Brain Res Mol Brain Res, 23, 163-78. http://www.sciencedirect.com/science/article/pii/0169328X94902232
LAMBE, E.K. & AGHAJANIAN, G.K. (2001). The role of Kv1.2-containing potassium channels in serotonin-induced glutamate release from thalamocortical terminals in rat frontal cortex. J Neurosci, 21, 9955-63. http://www.jneurosci.org/content/21/24/9955
MAREK, G.J., WRIGHT, R.A., GEWIRTZ, J.C. & SCHOEPP, D.D. (2001). A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex. Neuroscience, 105, 379-92. http://www.ncbi.nlm.nih.gov/pubmed/11672605
AGHAJANIAN, G.K. & MAREK, G.J. (1997). Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacology, 36, 589-99. http://www.ncbi.nlm.nih.gov/pubmed/9225284
AGHAJANIAN, G.K. & MAREK, G.J. (1999). Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release. Brain Res, 825, 161-71. http://www.sciencedirect.com/science/article/pii/S000689939901224X
MAREK, G.J., WRIGHT, R.A., SCHOEPP, D.D., MONN, J.A. & AGHAJANIAN, G.K. (2000). Physiological antagonism between 5-hydroxytryptamine(2A) and group II metabotropic glutamate receptors in prefrontal cortex. J Pharmacol Exp Ther, 292, 76-87. http://www.ncbi.nlm.nih.gov/pubmed/10604933
JONES, E.G. (2002). Thalamic circuitry and thalamocortical synchrony. Philos Trans R Soc Lond B Biol Sci, 357, 1659-73. http://www.ncbi.nlm.nih.gov/pubmed/12626002
Bortolozzi, A., Díaz-Mataix, L., Scorza, M. C., Celada, P. and Artigas, F. (2005), The activation of 5-HT2A receptors in prefrontal cortex enhances dopaminergic activity. Journal of Neurochemistry, 95: 1597–1607. doi: 10.1111/j.1471-4159.2005.03485.
Pablo Vázquez-Borsetti,Roser Cortés, and Francesc Artigas. (2009). Pyramidal Neurons in Rat Prefrontal Cortex Projecting to Ventral Tegmental Area and Dorsal Raphe Nucleus Express 5-HT2A Receptors. (DISCUSSION > FUNCTIONAL IMPLICATIONS). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693622/#__sec9title
Gottesmann C. (2002). The neurochemistry of waking and sleeping mental activity: the disinhibition-dopamine hypothesis. http://www.ncbi.nlm.nih.gov/pubmed/12109951
Mark Solms. (2000). Dreaming and Rem sleep are controlled by different brain mechanisms. Behavioral and Brain Sciences 23 (6):843-850 http://philpapers.org/rec/SOLDAR
GUILLERY, R.W. & HARTING, J.K. (2003). Structure and connections of the thalamic reticular nucleus: Advancing views over half a century. J Comp Neurol, 463, 360-71. http://www.ncbi.nlm.nih.gov/pubmed/12836172
VOLLENWEIDER, F.X. & GEYER, M.A. (2001). A systems model of altered consciousness: integrating natural and drug-induced psychoses. Brain Res Bull, 56, 495-507. http://www.ncbi.nlm.nih.gov/pubmed/11750795
Vankov, A., Hervé-Minvielle, A. and Sara, S. J. (1995), Response to Novelty and its Rapid Habituation in Locus Coeruleus Neurons of the Freely Exploring Rat. European Journal of Neuroscience, 7: 1180–1187. http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.1995.tb01108.x/abstract;jsessionid=DF78BCFD33EBFB9FCAE0CA502DA9ED63.d01t04?deniedAccessCustomisedMessage=&userIsAuthenticated=false
Sandra M Florin-Lechner, Jonathan P Druhan, Gary Aston-Jones, Rita J Valentino. (1996). Enhanced norepinephrine release in prefrontal cortex with burst stimulation of the locus coeruleus. Brain Research Volume 742, Issues 1–2, 2, Pages 89–97. http://www.sciencedirect.com/science/article/pii/S0006899396009675
AGHAJANIAN, G.K. (1980). Mescaline and LSD facilitate the activation of locus coeruleus neurons by peripheral stimuli. Brain Res, 186, 492-8. http://www.ncbi.nlm.nih.gov/pubmed/7357465
RASMUSSEN, K. & AGHAJANIAN, G.K. (1986). Effect of hallucinogens on spontaneous and sensory-evoked locus coeruleus unit activity in the rat: reversal by selective 5-HT2 antagonists. Brain Res, 385, 395-400. http://www.ncbi.nlm.nih.gov/pubmed/3096493
RASMUSSEN, K., GLENNON, R.A. & AGHAJANIAN, G.K. (1986). Phenethylamine hallucinogens in the locus coeruleus: potency of action correlates with rank order of 5-HT2 binding affinity. Eur J Pharmacol, 132, 79-82. http://www.ncbi.nlm.nih.gov/pubmed/3816969
- slapdancegraphics likes this
- thedevilwouldfuckme reblogged this from psymeow
- myheartisyoung likes this
- t-m3rma1d likes this
- roamingson reblogged this from disregardeverythingisay and added:
- roamingson likes this
- demilitarizedzone likes this
- wickedcadence likes this
- drakoolich reblogged this from disregardeverythingisay and added:
- sleep-market likes this
- thesilverspiral reblogged this from disregardeverythingisay
- thesilverspiral likes this
- free-your-brain likes this
- goodgoodgod likes this
- yureistargazer reblogged this from psymeow and added:
- wouldn-tgivemethenameiwanted likes this
- purplepsychedelia likes this
- radiokiin likes this
- fenou-dreamflame likes this
- jedermenschistzuviel likes this
- lmnopour-grammer likes this
- russhasa reblogged this from disregardeverythingisay
- queriousity likes this
- wudnbrane likes this
- strygoii reblogged this from disregardeverythingisay
- famemoose reblogged this from disregardeverythingisay
- zhaozhou likes this
- morphetamine likes this
- dumb-white-male likes this
- dapperanddishevelled likes this
- mindcrafter reblogged this from disregardeverythingisay
- mindcrafter likes this
- sketchydesires likes this
- thatfaceagain likes this
- itsonlyafabrication reblogged this from disregardeverythingisay and added:
- dirtfruit likes this
- famemoose likes this
- morphetamine reblogged this from disregardeverythingisay and added:
- hipstershatehipsters likes this
- hidingfromthenormals likes this
- cultmasterflash reblogged this from disregardeverythingisay
- thereignsofcashmere likes this
- zenesthesia reblogged this from disregardeverythingisay and added:
- dosedorsomething likes this
- goodbyeblueskyyyy reblogged this from disregardeverythingisay
- goodbyeblueskyyyy likes this
- benigndeviance likes this
- karmaeiic likes this
- psymeow reblogged this from disregardeverythingisay
- psymeow likes this