Physiological Action of Anhalonium Alkaloids

The Physiological Action of the Alkaloids Derived from Anhalonium Lewinii

By Walter E. Dixon, M.D., B.Sc. Lond., Salters' Company Research Fellow at St Thomas's Hospital

Anhalonium Lewinii, so called from its discoverer, Lewin, who in 1888 first directed attention to it, belongs to the small group of Melocacteae, and is native to Mexico... The genus Anhalonium is easily distinguished from Echinocactus and Mamillaria in being quite free from spines.

A. Lewinii is a small cactus, having roughly the shape and size of a radish. It is spoken of familiarly by traders in Mexico as "Mescal," and is occasionally confounded with another "Mescal" in Arizona, the "Agave," from which the Apaches prepared an intoxicating drink.

It has long been known that the Kiowa and other Mexican Indians ate some substance in their religious ceremonies which was stated to possess remarkable physiological properties, but in proportion as it was held sacred by the Indians it was condemned by the early missionaries and its exportation was prohibited.

The plant first attracted attention on account of its vision-producing properties, which all observers agree it possesses, and most of the literature on the subject which has already appeared consists principally in detailed accounts of these phenomena.

[A history of the chemical isolation of the plant's alkaloids by Lewin and by Heffter, and an extended account of the drug's actions on the circulation, respiration and other organ systems of frogs, cats, dogs and rabbits, are omitted here.]

The animals used in these experiments have been principally dogs and cats, but investigations have also been made on herbivorous animals, and as far as practicable on the human subject.

[Detailed clinical notes on salivation, perspiration, pupillary and reflex changes in human subjects are omitted.]

As in cannabis indica, time is over-estimated, possibly as a result of the rapid flow of ideas and the inability to fix the attention. Perception of space is also modified, on one occasion giving the impression that the ground sloped away in all directions.

Perception may be considerably delayed; for example, one may look at a person one knows well, and it is only after scanning his features for what appears to the experimenter a considerable time, that recognition occurs... The attention cannot be fixed, as the least stimulus is sufficient to alter the train of thought; thus it was found impossible to fix the attention on a book, and a subsequent examination of notes attempted during intoxication showed incoordination both as regards language and writing.

On two occasions when deeply under the influence of the drug, there was an indescribable feeling of dual existence; thus, after sitting with closed eyes subjectively examining the colour visions, on suddenly opening them for a brief space one seems to be a different self, as on waking from a dream we pass into a different world from that in which we have been.

But by far the most remarkable of these subjective phenomena are the sensory hallucinations, especially visual. These arise gradually, and are at first only seen with closed eyes: in the early stage (in my case) they closely resemble an attack of megrim, in that they show the same undulatory motion of zigzagged lines. The visions rapidly become more marked, until on closing the eyes a regular kaleidoscopic play of colours can be seen with either eye, precisely the same; hence the condition must be central.

These colours may assume all kinds of fantastic shapes; they are never still, but constantly in motion, sometimes in a circular or to-and-fro manner, but more generally there is a kind of pulsation somewhat similar to that in the cinematograph. It is interesting to note that pressure to the eyeball was sufficient to alter the colours and change the type of vision. In no case were visions of external objects seen, but always the same dashes of colour, of a brilliance and blending which in the intoxicated condition one considered of indescribable beauty, and even as a memory still seem to possess a charm. The colouring of all external objects is intensified. The light blue shadows seen with the eyes open in this stage are, as suggested by Ellis, probably due to dilatation of the pupils.

The effect of the sound of the piano was most curious and delightful, the whole air being filled with music, each note of which seemed to arrange around itself a medley of other notes which appeared to me to be surrounded by a halo of colour pulsating to the music.

Nasal hyperaesthesia was also present, though less evident than either the visual or auditory phenomena.

[Further sections on the drug's diuretic action, its excretion in the urine, and the results of animal dosing experiments recorded in numbered tables, are omitted.]

Experiment VI

Healthy adult man. Weight 11 stones. 0.25 gramme alkaloid taken by mouth (roughly an amount equivalent to two buttons), 12 o'clock. Before, pulse 73, respiration 17.

[Notes on pulse and respiration through the early hours of the experiment are omitted.]

...of external objects appears particularly vivid, and some scent sprinkled on a handkerchief seemed at times peculiarly strong and penetrating. Pupils well dilated and act sluggishly to light. Feel a strong desire to lie down.

2.30 p.m. Feeling of nausea quite disappeared, but there is a sense of oppression on the chest, and the respiration 35, shallow, with occasional deep sighs. I now experienced an extraordinary idea of unreality; I seemed to be having a dual existence — one in which I was subjective to all external and internal impressions (colour visions, etc.), and a second existence quite indescribable, in which I seemed to watch myself mentally in this subjective state. My hands now were tremulous; knee jerks increased. On walking I seemed to be "treading on air," and was ataxic. My voice became a little hoarse, auditory hyperaesthesia caused starting readily on slight noises. Intellection and introspection seemed to me unimpaired.

3 p.m. On seeing a friend I tried to be natural, but found myself asking him for the third time if he were all right. Fresh thoughts constantly rushed through my mind, and before I could complete a note I often forgot what I was writing about.

4 p.m. Took some food. Feeling more sober. My spirits very exuberant. Visions fading, respiration normal, heart 75.

10 p.m. Still some dilatation of the pupils, and the curious feeling of exhilaration. After-effects were principally insomnia. No noticeable effect on bowels or urine.

[A comparative discussion of the alkaloid's action on frogs, and further chemical and pharmacological analysis, is omitted.]

It must therefore be concluded that Mescal acts differently from any other known substance, although in isolated properties it resembles many. Cannabis indica, which at first it was thought most closely to resemble, differs from it in the delusions of merriment and in its hypnotic effect, whereas Mescal never gives rise to merriment, but rather to a condition of ideal content, and produces wakefulness.

To strychnine it is closely related by its marked effect on the brain and cord, but whereas strychnine acts mainly on the cord, the effect of "Mescal" is mainly cerebral and opisthotonos never occurs.