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persisting longer, and rarely passing into a longschizophrenic illness, are very hard to interpret. Forone thing, as LEWIS points out, many of the publishedreports made it clear that cannabis was not the onlydrug concerned. Moreover, the history of the patient’sformer mental state was often slender and the diagnosticmethods inadequate. Nevertheless, the lack of reliableinformation on the psychotic effects of heavy doses isone of the strongest reasons for retaining legal restric-tions on cannabis: " there is a need methodically toinvestigate possible cases of cannabis psychosis and, inparticular, to study the concomitant effect of other

drugs and of the abuse of alcohol in these cases."Evidence that a high proportion of heroin addicts

have previously taken cannabis does no more than

suggest that the marihuana smoker is more likely thanthe non-smoker to take to heroin: the frequency ofsuch a progression remains obscure. Any pharmaco-logical action prompting the cannabis-user to resort toother drugs is generally discounted. One of thecommonest explanations offered for a cannabis-heroinlink is that cannabis-users must inevitably turn fortheir supplies to the criminal underworld where opiatesare also available. Yet, the report finds,

"

according toour witnesses supplies of cannabis in this country arenot necessarily obtained in the same places as heroin ";but the committee certainly does not discount socialmixing of cannabis and opiate users as one mechanismof progression. The greatest emphasis lies, however,on the personality of the user: most heroin addicts aremultiple-drug users and come from the emotionallyimpoverished family background often found in otherdelinquent groups, and cannabis-users with similar

personalities and backgrounds may be predisposed tothe taking of heroin, amphetamines, and other drugs.The most that can be said of the few published inquiriesin the United Kingdom is that none have demonstratedsignificant lines of progression; and, taking into accountthe world picture, the committee decided that risk ofprogression to heroin is not a reason for retainingthe control over cannabis.

The decision to recommend a reduction in the

penalties for unlawful possession of cannabis is the

right one, though it is being vigorously contested. Wehope that forecasts of its rejection by the Home

Secretary will prove false. The situation in which, in1967, about a quarter of all cannabis offenders and 17%of first offenders were sent to prison should not con-tinue. Of 2419 persons who were convicted of possess-ing less than 30 g. of cannabis, 375 (15%) were

imprisoned. Average fines for possession offences in1967 were E36 for cannabis, E39 for other dangerousdrugs, and E28 10s. for drugs covered by the 1964 Act(amphetamines and L.S.D.). The discrepancies betweenthese figures and the relative dangers of the drugsconcerned led the committee to propose that possessionof a small amount of cannabis should not normally beregarded as a serious crime to be punished byimprisonment. Unlawful possession, sale, or supplyshould be punishable on summary conviction by a

fine not exceeding El 00 or imprisonment for not morethan four months or both (the present limits are E250and/or twelve months). On conviction on indictmentthe penalty should be an unlimited fine or imprison-ment for not more than two years or both (at presentthe courts can impose a E1000 fine and/or ten years). Theoffence of permitting premises to be used for smokingcannabis should be redefined so as to apply only topremises open to the public and to remove the absolutenature of the liability on managers. The report alsoadvises a review of police powers of arrest and searchin relation to drug offences generally, since anyreduction in penalties for cannabis possession wouldraise the question of relaxing police powers to searchfor it. Two members of the subcommittee expressedreservations about these proposals. Mr. P. E. BRODIE

preferred a heavier penalty (unlimited fine and/or fiveyears on indictment) in circumstances where traffic inlarge quantities of cannabis is established. Mr.MICHAEL SCHOFIELD wanted the distinction between

possession for use and possession for supply writteninto the law, with a maximum fine of E50 and no

imprisonment on first or subsequent conviction forillicit possession of up to 30 g., this to be a summaryoffence only. He also maintained that existing extensivepolice powers of search and arrest were not necessary,since " taking cannabis in moderation is a relativelyminor offence."

Five years ago The Lancet suggested 3 that the

argument for legalising the import and consumption ofcannabis was " worth considering "; and we examinedat that time some of the pros and cons now discussedin detail and with later information by Lady WOOTTONand her colleagues. That phrase,

" worth considering ",was unhappily interpreted by many who had not readthe whole of our 1963 leader as an announcement of

support for legalisation; and it has been quoted in thatsense from time to time ever since. We did not and donot advocate the removal of all restrictions. Never-

theless, in the words of the report, "we do not

entirely discount the possibility that properly organisedresearch may one day produce information whichcould justify further consideration of the practicalproblems of legalisation."

Mechanisms of MemoryTHE storage of each new bit of information in the brain

presumably depends on a more or less permanentchemical change in a group of neurons; and if the brainis to do its classification-selection job efficiently, this

change must result in the facilitation of that particularneuronal pathway (or, as YOUNG 4 suggests, the inhibi-tion of unwanted pathways). The analogy between, say,the human brain and a computer is somewhat crude; butso is our knowledge of the chemical activity of the brain.A few years ago D.N.A. and R.N.A., because of their infor-

mation-carrying ability, were tentatively cast in the role3. Lancet, 1963, ii, 989.4. Young, J. Z. Memory System of the Brain. London, 1967.

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of memory molecules, and reports of improved learningand retention in rats fed on an R.N.A.-supplementeddiet were therefore received with some enthusiasm.Later trials, however, were less encouraging. Oral orintravenous administration of R.N.A. to patients withmemory loss associated with arteriosclerosis or seniledementia 6-10 were inconclusive. The beneficial effect ofR.N.A., if any, lasted only as long as the period ofadministration and may have been no more than anon-specific stimulus. This is probably true, also, of thereported saving in training time in planaria fed ontrained flatworms or injected with brain extracts fromtrained worms. (These experiments are in any case ofdoubtful value, since some workers have been unableto train planaria to a consistent level of performance.")These disappointing results are not really surprising,

nor is the fact that labelled R.N.A. has never been shownto become incorporated into brain cells 12; for it is

unlikely that such a large molecule could penetrate thebrain cells without being broken down. That is not tosay that R.N.A. is not involved in memory in some way:it would be more surprising if it were not, so abundantis it in nerve-cells. HYDtN,13 among others, has reporteddifferences in the base ratios of ribonucleotides between

groups of about 300 cells isolated from the brains oftrained and untrained rats. He also reports that duringpassive stimulation the R.N.A. content of the neuronsincreases but that of the glial cells falls; whereas inlearning both neuronal and glial R.N.A. increases. In

planarians, CORNING and FxEED 1 found an unusuallyhigh turnover of R.N.A. during training, although thefinal R.N.A./D.N.A. specific activity ratios were similar intrained and untrained worms. HYDEN and LANGE 15demonstrated that early in learning a small amount ofuracil-rich R.N.A. is synthesised, R.N.A. rich in guanineand cytosine appearing later. These workers suggestthat the changing bases might be related to short-termand long-term memory formation.Protein synthesis has also been implicated in memory

formation, but, as with R.N.A., its role is uncertain.Intracerebral injection of antibiotics, which are known toinhibit protein synthesis, also interferes with theestablishment of long-term memory in mice. BARONDESand COHEN,16 for instance, found that mice injectedwith puromycin immediately before training in a

T-maze learned normally and remembered normally forabout 3 hours, but within 6 hours of training theirretention of the task was greatly and permanentlyimpaired. BARONDES and COHEN concluded that protein5. Cook, L. in Animal Behaviour and Drug Action. London, 1964.6. Cameron, D. E. Am. J. Psychiat. 1958, 114, 943.7. Cameron, D. E., Solyom, L., Beach, L. Neuropsychopharmacology, 1961,

2, 351. 8. Cameron, D. E., Sved, S., Solyom, L., Wainrib, B., Barik, H. Am. J.

Psychiat. 1963, 120, 320.9. Cameron, D. E., Solyom, L., Sved, S., Wainrib, B. in Recent Advances

in Biological Psychiatry. New York, 1963.10. Wolff, K. Int. J. Neuropsychiat. 1965, 1, 216.11. Calvin, W. in Brain Function IV (edited by D. B. Lindsley and A. A.

Lumsdaine); p. 21. Los Angeles, 1967.12. John, E. R. in Mechanisms of Memory. New York, 1967.13. Hydén, H. in The Neurosciences (edited by G. C. Quarton, T.

Melnechuk, and F. O. Schmitt); p. 248. New York, 1967.14. Corning, W. C., Freed, S. Nature, Lond. 1968, 219, 1227.15. Hydén, H., Lange, P. W. Proc. natn Acad. Sci. U.S.A. 1966, 53, 946.16. Barondes, S. H., Cohen, H. D. ibid. 1967, 58, 157.

necessary for long-term memory was synthesised duringor within minutes of training. Unfortunately, puromycindepresses the electrical activity of the brain, and it couldwell be this effect, and not the inhibition of proteinsynthesis, that interferes with memory. BARONDES andCOHEN 17 have done similar experiments with acetoxy-cycloheximide, which blocks protein synthesis withoutdepressing brain activity. This drug, like puromycin,impaired long-term memory, but only when given inmassive doses. GAMBETTI and his colleagues 18 havepointed out that puromycin blocks memory indefinitely,whereas acetoxycycloheximide’s effect is short-lasting;and they suggest that the differing effects of these twodrugs may be related to the different stages at whichthey block protein synthesis. Puromycin prevents theassembly of aminoacids on the ribosomes and causesdisaggregation of polysomes. It also causes swelling ofneuronal mitochondria, probably through the action ofpeptidyl-puromycin complexes, and GAMBETTI and hiscolleagues think that this action of puromycin onneuronal cellular (or intracellular) membranes may berelated to its effect on memory. The results of another

experiment in rats described by HYDEN and LANGE 19add weight to the view that protein synthesis is increasedduring learning. Electrophoretic separation of minuteamounts of protein from small groups of hippocampalcells after intraventricular administration of 3H-leucineshowed that protein synthesis of two fast-moving frac-tions was significantly higher in trained than inuntrained animals. However, the specificity of the

protein could not be identified.

Although earlier transfer experiments were criticisedon the grounds of non-reproducibility and possibility ofnon-specific effect, the experiments of UNGAR and hiscolleagues 20 meet both challenges. Intraperitonealinjection of mice with brain extracts from rats trainedto prefer light to dark enclosures (a reversal of thenormal behaviour of both animals) produced in therecipients a definite preference for light surroundings,whereas brain extracts from untrained rats had nonoticeable effect. The degree of learning transfer

depended on the amount of extract injected, the lengthof training of the donors, and the interval betweentraining and removal of the brain. To investigatethe chemical properties of the transfer factor, extractswere incubated with 3 enzymes. Trypsin abolishedthe transfer effect; chymotrypsin and ribonucleasehad no effect. UNGAR and his colleagues concludethat the transfer factor is probably a basic peptide withbetween 6 and 10 aminoacid residues-a size which,they suggest, would carry enough information to securethe new neural connections required for most types oflearned behaviour.

An immunological technique described by JANKOVIC’and his colleagues 21 is one of the more promisingdevelopments in the study of memory, for antibodies to17. Barondes, S. H., Cohen, H. D. Science, N.Y. 1968, 160, 556.18. Gambetti, P., Gonatas, N. K., Flexner, L. B. ibid. 1968, 161, 900.19. Hydén, H., Lange, P. W. ibid. 1968, 159, 1370.20. Ungar, G., Galvan, L., Clark, R. H. Nature, Lond. 1968, 217, 1259.21. Janković, B.D., Rakić, L. J., Veskov, R., Horvat, J. ibid. 1968, 218, 270.

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brain proteins should affect the neurons in a highlyspecific way. Injection of rabbit anti-cat-brain antiserainto the cerebral ventricles of cats previously conditionedto make a leg movement in response to a certain soundcaused a sharp drop in the level of performance whichlasted at least 27 days. Cats injected with anti-liverantibodies showed no deterioration in performance.The value of these experiments will be greatly increasedif the antigens to which the antibodies are prepared canbe precisely identified and separated.The main result of these various experiments has been

to emphasise how little we know about the mechanismof memory. Observed changes in R.N.A. turnover orprotein synthesis tell us nothing about the subcellularchanges which take place-whether, for instance,facilitation entails a change at the synapses (perhapsthrough a change in cell-membrane permeability) orincreased output of transmitter substances. At the otherend of the scale, we cannot begin to translate thebiochemical findings into emotional terms. Most of ourinformation comes from studies on conditioned reflexesformed by repeated presentation of a single stimulusreinforced by reward or penalty; and these give littleinsight into the way in which memories associated withrecognisable emotions are retained, why some par-ticularly unpleasant memories may be repressed, or whysome trivial events are remembered and not others.

Vomiting.

--------0

As a dog returneth to his vomit, so do physicians(psychiatric and electrolytic) return to the subject ofvomiting. To the question

" What’s new in vomiting ? "one might reply that when cosmonauts do it, it appearsto make news; but on a more terrestrial level it must beadmitted that there is still a good deal to be learned aboutthe causes and consequences of vomiting. Last yeara paper 1 in these columns displayed the value of inter-national cooperation in research, as well as the extent ofthe secondary consequences of recurrent vomiting.WoLFF and his colleagues laid emphasis on the variousways in which unhappy women can contrive to loseelectrolytes and to conceal that they are doing so.

WRONG and RICHARDS 2 mentioned two male patientswhose electrolyte disturbance

" seemed to be solely dueto surreptitious vomiting "; and the promised report 3on these patients which has now appeared containsfeatures of metabolic, endocrine, and psychiatric interest.At the turn of the year, we may be allowed nostalgically

to recall the age of electrolytic innocence, when loss of" acid " in the gastric juice led naturally and simply to" alkalosis ". This deceptive simplicity was firstbreached by the evidence that, despite the low concentra-tion of sodium in gastric juice, depletion of sodium wasthe basis of circulatory disturbance associated with

pyloric stenosis.4 This observation of GAMBLE was one1. Wolff, H. P., Vecsei, P., Krück, F., Roscher, S., Brown, J. J.,

Dusterdieck, G. O., Lever, A. F., Robertson, J. I. S. Lancet, 1968, i, 257.2. Wrong, O. M., Richards, P. ibid. p. 421.3. Wallace, M., Richards, P., Chesser, E., Wrong, O. M. Q. Jl Med. 1968,

37, 577.4. Gamble, J. L., Ross, S. G. J. clin. Invest. 1925, 1, 403.

of the earliest demonstrations that it is not only what islost that matters but also the relative efficiency of theadaptations which the body can make to an alteredsituation. This was carried a stage further when itbecame clear that correction of sodium depletion, bythen well recognised, might permit the development ofsignificant depletion of potassium, again in patients withpyloric stenosis.5 This is only partly due to loss of thesmall amount of potassium in gastric juice; it is mainlyrelated to loss in the urine. Both of WRONG’S patients 3excreted large amounts of potassium; and he rightlysays: " This feature cannot be regarded exclusively asevidence for primary renal or adrenal disease, for it ischaracteristic also of the hypochlorxmic alkalosis causedby loss of gastric hydrochloric acid ". Ten years agothe emphasis lay, or had lain successively, on the cationshydrogen, sodium, and potassium; it was left to

SCHWARTZ and his colleagues to re-emphasise the

importance of the anion chloride. Having previouslyshown that even respiratory alkalosis could not be fullycorrected without supplying chloride,’ they found thatalkalosis induced in volunteers by gastric aspiration alsorequired chloride for its correction.8 Clinical observa-tions pointing to the important role of chloride in

correcting alkalosis have also been reported.9 9 Thewhole question of the role of anions in metabolicalkalosis has recently been reviewed by Schwartz andhis colleagues.10

In the studies of alkalosis induced by gastric aspiration,it was noted that potassium was poorly conserved,whereas conservation of sodium remained efficient.KASSIRER and SCHWARTZ 8 attributed this to an alterationof tubular function, consequent on a lower concentrationof chloride in the tubular fluid; but a similar shift frompotassium to sodium conservation could be the con-sequence of increased activity of aldosterone, one ofwhose actions is to increase the exchange of sodium forpotassium in the distal tubule. It is of much interestthat psychogenic vomiting has now been found to beconsistently associated with raised levels of plasma reninand aldosterone, and an increased secretion-rate ofaldosterone.1 The increase in aldosterone activity is

presumably secondary to the stimulus of increased

plasma-renin; but the cause of increased renin formationis not fully established. One link in the chain may besupplied by the finding of hyperplasia of the juxta-glomerular apparatus in a renal biopsy specimen in oneof WRONG’S patients.3 This same patient was resistantto the pressor effect of intravenous angiotensin and hada high plasma-renin concentration; he thus resembled,presumably on a secondary basis, the patients describedby BARTTER," in whom overaction of the juxta-5. Burnett, C. H., Burrows, B. A., Commons, R. R., Towery, B. T.

ibid. 1950, 29, 175.6. Black, D. A. K., Jepson, R. P. Q. Jl Med. 1954, 23, 367.7. Schwartz, W. B., Hays, R. M., Polak, A., Haynie, G. D. J. clin. Invest.

1961, 40, 1238.8. Kassirer, J. P., Schwartz, W. B. Am. J. Med. 1966, 40, 10.9. Aber, G. M., Sampson, P. A., Whitehead, T. P., Brooke, B. N. Lancet,

1962, ii, 1028.10. Schwartz, W. B., van Ypersilc de Strihou, C., Kassirer, J. P. New

Engl. J. Med. 1968, 279, 630.11. Bartter, F. C., Pronove, P., Gill, J. R., MacCardle, R. C. Am. J. Med.

1962, 33, 811.