There are many factors that influence the effect and outcome of a drug, perhaps the most obvious ones being the type of drug, dosage, route of administration and preparation of the drug and equipment.

Cannabis will have a different effect to amphetamine, as will heroin to cocaine, and so on, but overall effects are generally agreed on, e.g., cannabis is relaxing, amphetamine is stimulating, but there are other factors to consider.
Dosage is an important consideration; in low doses cannabis has a relaxing, mildly disinhibiting effect, while at higher doses can produce feelings of paranoia, anxiety or distress. Heroin, in small, controlled doses would be unlikely to produce a fatal overdose, while a slightly larger dose just might.

Further is the route of administration of the drug. There are four main routes of drug use, involving the digestive, respiratory, membranal and circulatory systems of the body. A suitable example of potential effects and outcomes of different routes of administration is the differences between smoking and injecting heroin. When smoked, it is virtually impossible to overdose (the user is likely to nod off before a fatal dose can be ingested), whereas even small doses of an unfamiliar strain of heroin can produce a fatal overdose. The effects of injecting and smoking also vary in terms of sensations, with smoking there is no instant "rush" and the effect is milder. Smoking also reduces some of the health hazards associated with injecting such as the risk of disease through shared equipment, injury (including collapsing of veins, a long term heroin injector is a resus. team’s worst nightmare) through poor injecting technique and various other associated problems. However, some of these health hazards can be avoided or at least minimised by, e.g., careful preparation of the drug as appropriate and not sharing "works".

A most important variable encountered when evaluating the effects and outcomes of a drug is the interaction of the drug with the non-drug factors, set and setting. Set refers to the drug user’s biological make up including personality, past drug experiences, expectations of the drug effect and mood at the time of the drug experience. Setting refers to the external surroundings and social context in which the individual takes the drug. Set and setting exert their largest effect on psychoactive drugs with subtle, subjective mental effects and minimal physiological effect. Set and setting exert a variable but often marked influence on potential drug effects (Waskow etal, 70’s; Wickler, ‘70s).

A good example of set and its effects is the apparent "amphetamine paradox". Amphetamine is an effect treatment of hyperactivity in children, yet increases behaviour in "normals" (Bradley, ’37; Knight, ‘70s). Dews (’58) explained this phenomena in terms of his Rate Dependency Hypothesis, which states that the baseline rate of behaviour, part of "set", will largely determine the effects of a drug.

The effect of past drug use is evidenced by the phenomena of "reverse tolerance". Smith & Mehl (‘70s) reported that the novice cannabis user reports feeling no high or needs considerably more drug to get high on his first few trials than after he obtains more experience of the drug. Similarly, Goode (‘70s) found that more frequent and term users of cannabis tend to require fewer joints to get high. Lemberg and Mechoulam (both ‘70s) have suggested the possibility that enzymes necessary to convert THC to a more active compound requires prior use of cannabis.

Reverse tolerance appears to be a complex phenomenon. Jones (‘70s), presented evidence which stressed the importance of expectation, setting and prior drug experience on learning to get high. As the user gains more experience of cannabis, the more the individual’s mind is able to respond to the expectation of getting high. So much so that they actually became high when given an inert material which looked and smelled like cannabis. It should be noted, however, that several investigators, e.g., Hollister and Fink etal, ‘70s, found no evidence of reverse tolerance after repetitive daily use in experienced cannabis users.

Personality factors and mood when taking the drug are other important role players in the effect and outcome of a drug, e.g., the chances of a neurotic person or someone who is feeling depressed having a bad trip on LSD  are higher than for someone who is "balanced" and in a great mood.

The classic example of the role of setting in drug effect and outcome is Zinberg’s Vietnam Soldier study. Whilst in Vietnam a large percentage of soldiers became addicted to opium, but on return to the USA the majority of them ceased to use with many experiencing little, if any side effects. Zinberg relates this to the factors surrounding the drug use setting but, in further support of the effect of setting, this phenomenon can also be explained in terms of feed-forward mechanisms (the body "predicts", from environmental cues, e.g., the sight of a "works", that drug use is going to occur and prepares for change prior to ingestion of the drug, e.g., reduces endogenous opiate activity). Since the soldiers were in completely different environments on return to the USA, the usual environmental provokers may not have been present and, therefore, the probability of withdrawal is decreased. Such mechanisms also go some way in explaining how the same dose of a drug can kill a user when taken in unusual surroundings, giving further support to the influence of setting.

Other situational factors influencing effect and, particularly, outcome include the safety of the place where the drug is taken (safer to sniff gas in your bedroom than on the canal bank), the people you are with (smoking pot with strangers, e.g., may induce paranoia), and unforeseen events (such as your mother turning up or having to drive while on acid) amongst other things.

In many multivariate models, such as that of Cahalan and Room (‘70s), good predictors of alcohol problems include ethnicity, social class and setting variables, particularly the drinking habits of  our companions, which we are likely to be mimic. There are always exceptions to such findings, however.

Further variables of setting which influence drug effect and outcome are what Zinberg (’84) terms "social sanctions" (values and rules of conduct), and "social rituals" (patterns of behaviour), which together form social controls. Social sanctions may be informal, such as don’t drink and drive, or they can be formal, such as the laws around drug use. Such social sanctions serve to reduce the risk of potential crises, traffic accidents, for example. Social rituals are "stylised, prescribed patterns of behaviour" such as always buying from the same, "reputable" dealer (reducing risks associated with adulterated "gear"), always using a fresh works and disposing of it safely (minimising the risk of disease), never drinking alcohol after a "hit" (reduces the risk of overdose), etc.

All of the various sanctions and rituals imposed on the drug user by him/herself, society or law enforcement agencies, alongside the other discussed variables of drug, set and setting, will obviously have their effect on the outcome of using drugs and the effects of those drugs. To attempt to study the effects and outcomes of a drug without giving due consideration to all three variables, drug, set and setting, is to court accusations of totally inadequate examination and carelessness. Attempting to ascertain which of the three variables is the more important is verging on the impossible because they are each so heavily intertwined.

Louise Schofield 2000