Category:Metaphysica: Difference between revisions

The Metaphysica, the intimations, are the small set of medicines and materials Dale Pendell gathered, in the first volume of his Pharmako trilogy, under the heading of "intimations on the nature of things": substances that produce, in a small dose and a quiet room, the strong subjective sense of having glimpsed something true about the structure of reality.^[1] The anchor of the class is nitrous oxide, and the founding case is Humphry Davy in Bristol in 1799.

On a winter evening in 1799, at the Pneumatic Institution in Bristol, the twenty-year-old chemist Humphry Davy inhaled a sample of the gas he had synthesized, nitrous oxide, and discovered that he was laughing. He inhaled more. He discovered that the laughter gave way to a powerful sense of insight, and wrote, on returning to baseline: "Nothing exists but thoughts! The universe is composed of impressions, ideas, pleasures, and pains."^[2] Davy did not introduce nitrous oxide as an anesthetic, though he saw the possibility; that step would wait nearly fifty years, until Horace Wells in 1844. Davy introduced something else: the proposition that a gas, breathed in, could open a window onto the nature of being.

Eighty years later, the philosopher and psychologist William James experimented with nitrous oxide himself, and reported the same phenomenon in his characteristic prose: "Our normal waking consciousness, rational consciousness as we call it, is but one special type of consciousness, whilst all about it, parted from it by the filmiest of screens, there lie potential forms of consciousness entirely different."^[3] James added, with the chagrined honesty that defines his accounts of these experiments, that the insight refused to remain. He could write down a sentence that had seemed, in the gas, to capture everything; on returning to ordinary consciousness, the sentence read as nonsense. The metaphysical revelation, made by the gas, declined to be made by anyone else.

The other members Pendell groups here are less famous and more obscure. Leonotis leonurus, the lion's tail or wild dagga of southern Africa, has been smoked traditionally by the Khoikhoi and others; its psychoactive properties are mild and its pharmacology limited. Ivy, Hedera helix, is named in Pendell's catalog for an even thinner historical record of psychoactive use; the connection is more literary than pharmacological. The class is the smallest of any Pendell describes, and its centre of gravity sits on nitrous oxide.

• Nitrous oxide
• Leonotis leonurus (lion's tail, wild dagga)
• Hedera helix (common ivy, as catalogued by Pendell; the pharmacological case is thin)

Nitrous oxide acts at multiple molecular targets. Its primary action is non-competitive antagonism of the NMDA glutamate receptor, mechanistically related to ketamine and a likely substrate of its dissociative properties. It is also a partial agonist at endogenous opioid receptors, an action that contributes to its analgesic effect, and it potentiates GABA-A receptors at higher concentrations. Leonotis leonurus contains marrubiin and other diterpenoids of uncertain pharmacological action; the plant's effects in traditional use are reported as mild and brief. Ivy contains saponins of contact-dermatitis and gastrointestinal-toxicity relevance but no well-characterized psychoactive principle.

Nitrous oxide has been used as an anesthetic for over a century with a strong safety profile in the acute setting, but recreational use carries two distinctive dangers worth noting. The first is hypoxic injury during inhalation of pure or nearly-pure gas (as from a balloon or a charger directly inverted into the mouth), which can produce fatal anoxia with no warning. The second is subacute combined degeneration of the spinal cord, a B12-deficiency syndrome produced by nitrous oxide's irreversible oxidation of the cobalt atom in cobalamin; chronic heavy users develop a peripheral and central demyelinating neuropathy that can be irreversible if not caught early.^[4] Leonotis leonurus has no well-documented serious toxicity in traditional use; ivy ingestion is genuinely dangerous because of saponin content and is not used recreationally in any tradition the wiki recognises.

As with all medicines, figures for these risks are population estimates that vary between studies, and individual response varies considerably between people.