Brief Primers on the Neuroscience of Psychedelics 3: The Tropanes
Why are Datura, Belladonna, and Mandrake psychedelic (deliriant)?
Tropane-containing plants have a history as intoxicants reaching back to pre-Bronze Age eras more than 5,000 years ago. In Europe, mandrake and henbane have historically played roles as the major active constituents of witches’ ointments, allowing them to communicate with spirits, demons, and perhaps even Old Nick himself. Plants of the Datura and closely-related Brugmansia genus — specifically Datura innoxia (Toloache) and Datura stramonium (Thorn Apple) — have roles in the sacred rituals of the New World.
Three closely-related tropane alkaloids are responsible for the psychoactive effects of these plants. Atropine, hyoscyamine (one optical isomer of atropine), and scopolamine (also known as hyoscine), which is thought to be primarily responsible for the unique psychedelic state induced by these plants.
The tropane alkaloids are notable in that they often elicit what are called true hallucinations — these aren’t visions that are recognisable as such, but hallucinations that blend perfectly with the environment. With the classic psychedelics, the user is, more often than not, aware that their eyes-open visuals are distinct from the normal waking world. However, this is not always the case with the tropanes. When consumed orally, the effects are often delayed and can sneak up on the user, who might assume the plant to be inactive, only to realise some time later that they spent the preceding two hours entertaining guests at a party that never happened. In this way, tropane intoxication is often likened more to a waking dream than a psychedelic trip:
“I remember walking around my dorm thinking I was naked, and there were at least 10 people in every room… We all talked for what seemed like years, discussing many things from the roman empire to how butterscotch was made.” (Erowid Experience Vault, #93015)
None of these people existed.
However you choose to define the tropane state, there’s clearly something very strange going on inside the brain that’s quite distinct from the effect elicited by the classic psychedelics. To understand this, we need to think about the way the brain builds and tests its world model against sensory information. Refer to Primer 1 on the classic psychedelics for a recap if necessary:
In brief, although you feel like you’re in direct contact with the external environment, your waking world is actually a model of the environment built by your brain from patterns of information generated by your cortex. Your brain continuously tests this model against the environment by attempting to predict the flow of sensory information it’s receiving. Correctly predicted sensory information is “extinguished” or filtered out, meaning it isn’t passed into the cortex for processing (which is expensive!).
Whenever the brain fails to model the unfolding of events in the environment, these predictions also begin to fail. This mismatch between predicted sensory information and actual received sensory information generates error signals, which flow into the cortex. The brain then updates its model until those error signals decline.
However, this somewhat oversimplifies the problem the brain must overcome in building a successful model, since it assumes that sensory information is always perfectly reliable. In other words, if a sensory prediction is unfulfilled, does this necessarily mean the model is flawed? What if the sensory information is itself flawed and isn’t providing reliable information about the environment? Can your brain always trust the sensory information it’s receiving?
Visual sensory information entering the brain is also inherently noisy and cannot be assumed perfectly reliable. Under low-light conditions or when light is obscured by fog, for example, noise levels are even higher, further decreasing the quality of visual sensory information. Fortunately, as well as learning the patterns and regularities in the patterns of sensory information, your brain has also learned that it must *expect* varying levels of random fluctuation in sensory information and, consequently, the low-level prediction errors this noise generates. Sensory noise is, by definition, unpredictable and, as such, even a perfect model of the environment is unable to predict these random fluctuations. In other words, low-level prediction errors are unavoidable, even when the world model and its predictions are working perfectly. The cortex ought only to update its world model if there’s good evidence that it’s failing. Prediction errors resulting from low quality sensory information and random noise isn’t good evidence.
By learning how much of this noise-generated prediction error is to be expected under different conditions (low light, fog, etc), your brain can assess whether a particular pattern of prediction error is likely to be newsworthy and indicative of important unpredicted changes in sensory information or, conversely, if it can safely be ignored. The more noisy and unreliable sensory information becomes, the less your brain is able to trust it, and the more it relies upon its internally-generated model.
Information judged to be reliable ought to be allowed to enter the brain more freely than unreliable information, and your brain has evolved mechanisms to control the flow of predictions errors (and thus sensory information) depending on how reliable it considers them to be. If the prediction errors are deemed reliable, then the “volume” of the prediction errors is kept high. On the other hand, under conditions in which these predictions are less reliable (such as a dark and foggy night), the volume of the errors is turned down and the brain must rely more heavily on its internal world model.
A subtype of receptor for the neuromodulator acetylcholine — the muscarinic M1 receptor — has an important role in controlling the “volume” of error signals as they flow into the cortex. These M1 receptors are found on the neurons responsible for transmitting the error signals through the cortex. When activated by acetylcholine, M1 receptors make the neurons more excitable, effectively increasing the strength of the error signals. So, the cortex can regulate the flow of prediction errors by increasing and decreasing the level of acetylcholine that reaches these neurons.
The tropane alkaloids bind strongly to the M1 receptors without activating them — they act as antagonists, blocking the activation by acetylcholine. This dramatically lowers the volume of the error signals even when sensory information ought to be judged as highly reliable.
Muting of the error signals results in the brain’s world becoming divorced from the environment, since it no longer receives the results of its prediction tests. Errors are never corrected. Entirely fantastical ideas can become incorporated into the world model and remain stable for long periods of time without protest from error signals. This is why the experience is often described more as a delirium or waking dream than a psychedelic trip, since a dream is precisely a world built by your brain when it’s disconnected from the environment (during sleep).
In contrast, at regular “open eyes” dose levels of the classic psychedelics (LSD, psilocybin, DMT), when navigation and exploration of the external environment remains possible, visions/hallucinations tend to be transient and unstable, quickly giving way to new forms and structures as error signals (which aren’t muted by the classic psychedelics) force model updates. The classic psychedelic visions announce themselves as being distinct from the stable and familiar waking world. Tropane visions do no such thing.
“Next thing I know its already 6:46am and I am running late. My mom tells me I only got a half hour to get ready or ill get a Saturday detention. I scramble out of bed and run into the bathroom to take a shower… Then I run into my room and get dressed and go downstairs to the kitchen. Right then I noticed something was wrong, the clock said 1:00am and the calendar was on July. No body was up. My mom was asleep and had been asleep. She didn’t wake me up for school, I did not have school in summer.” (Erowid Experience Vault, #16996)
“Phantom smoking” is a curiously common effect reported after consumption of tropane-containing plants. Trippers will not only smoke an imaginary cigarette for extended periods of time but then, finally noting its absence, scramble around on the floor searching the ‘dropped cigarette’ before it should set the house alight. See this news report showing this effect:
When a tropane user “smokes” a phantom cigarette, the user’s world model contains that cigarette in precisely the same way that their normal waking world contains a cigarette when they’re actually doing so (the same applies when smoking in a dream!). The difference lies in the relationship the cigarette model has with the environment. When error signals are muted by the tropane molecules, the model loses its moorings and becomes detached from the environment, which is unable to provide a challenge to the veracity of this entirely bogus, self-generated, non-functional model. But the cigarette model is the same. Of course, this also applies to hallucinated people and even entire scenes which can play out for long periods of time as if in normal waking life.
For most people, the tropane intoxication is not particularly pleasant or worthwhile and the inherent toxicity of these alkaloids means they can’t be recommended. Further, unlike dreaming, in which the dreamer’s motor function is mercifully inhibited to save them acting out their dreams, there is no such mercy for the tropane tripper, who will often begin interacting with the non-existent people and objects in their own private fantasy world. To an outside observer — a trip sitter is obviously highly recommended if you choose to use the tropanes — the tripper’s behaviour will often appear frighteningly bizarre, and it’s often at this point that medical assistance is sought. Unfortunately, the motives and intent of anyone attempting to assist the tripper will likely be entirely unappreciated, and attempts at encouraging or coercing them tend to be met with resistance or, in some cases, outright violence. The tropanes are not to be played with.
For a much more detailed discussion and explanation of the neurological mechanisms behind the tropane alkaloids, please refer to my latest book, Reality Switch Technologies: Psychedelics as Tools for the Discovery and Exploration of New Worlds, which covers all the major classes of psychedelics in unprecedented depth and detail. See my website for more details:
https://www.buildingalienworlds.com/books.html