Introduction
Amphetamine was widely prescribed until the mid 1960s as a
stimulant and appetite-suppressant, until the
dependence-potential of amphetamine (and other stimulants) led
to a falling out of favour among the medical profession.
Amphetamine, although a controlled drugs, is still prescribable
for certain conditions (e.g. narcolepsy), and appears in
Schedule 2 of the Misuse of Drug Regulations 1985, meaning that
it can be prescribed for medical treatment subject to proper
monitoring and reporting criteria.
Amphetamine is a powerful central nervous system stimulant drug,
used recreationally for the euphoriant effects, as well as ‘functionally’
to ward off fatigue and increase energy and capacity for
physical activity. The effects of amphetamine are similar to
those of cocaine, both affecting the same neural systems,
amphetamine stimulates catecholamine release, and cocaine
reduces reuptake - expressed simply, if the level of alertness
were to be represented by the water level in a bath, amphetamine
would act by turning on the taps, whereas cocaine would act by
putting in the plug.
The effects of amphetamine have been studied for over a century,
although since it became a controlled drug in most countries of
the world, opportunities for research on the effects on humans
have been limited.
Animal Studies
Animal studies have consistently found stimulant drugs such
as amphetamine and cocaine may cause analgesia (typically
measured by the length of time an animal takes to respond to a
painful stimulus).
Mice: Natsuoka et al reported "analgesic actions ((of
amphetamines) involve the participation of endogenous serotonin
and endogenous opioid peptides" Furst suggested a
relationship between the stimulant neurotransmitter systems and
opiate analgesia. A Russian study suggests the analgesic effects
may be influenced by psychosocial factors. Amphetamine was found
to decrease depression of swimming endurace in mice treated with
opiates, suggesting the (similar/synergistic) analgesic effects
may be differentiated from the (opposite/antagonistic)
psychoactive effects of the two drug types. As with humans,
tolerance to the analgesic effects of both amphetamine and
morphine are reported in mice.
Rats: Studies in rats have suggested amphetamine-like compounds
can induce analgesic (pain-killing) effects potentiating the
analgesic effects of opiates, and that analgesia from
amphetamine may be counteracted by dopamine antagonists - Clarke
et al concluded: "dopamine innervation of the nucleus
accumbens... plays a major role in the analgesic effect of
amphetamine" - or by destroying the dopamine-producing
cells in brain-stem nuclei. However, earlier studies suggested
noradrenaline rather than dopamine to be the mediating
neurotranmitter for amphetamine enhancement of opiate analgesia,
that amphetamine analgesia did not involve endogenous opiates
such that "amphetamine possesses intrinsic analgesic
properties".
The contrasting effects on alertness of opiates and amphetamines
have been widely-noted: Borisenko, studying behavioural effects
and pain relief from opiates and amphetamine, reported "the
analgetic action and that activating the positive emotion were
independent effects of the psychotropic agents.". The
reversal of narcotic-induced depression by amphetamine was also
noted by Malec et al and Lakin Et al. Miksic et al considered
there to be two distinct neural mechanisms underlying the
effects of analgesia and euphoria.
Sasson et al considered in 1986 that "opiate analgesia is
potentiated by concomitant d-amphetamine administration. The
mechanisms involved in this potentiation warrant further
investigation for the clinical management of pain."
Human Studies
In 1979, Shimm et al studied pain management in chronic
cancer patients anc concluded "Stimulants such as cocaine
and amphetamines both potentiate narcotic analgesia and reduce
narcotic-induced somnolence and respiratory depression" A
1967 study found the analgesic affect of aspirin to be modified
by amphetamine.
Studying healthy male volunteers, Webb et al found amphetamine
and a non-opiate analgesic both increased pain thresholds, the
combination providing the greatest relief.
Jaskinski et al found the combination of amphetamine and
morphine to create greater euphoria among substance-abuser than
either drug alone, although the psychological effects
(stimulation, drowsiness) were mutually attenuated, considering
there to be a greater degree of abuse potential from the
combination of the two drugs.
In a treatise on cancer pain, Mancini et al reported: "Many
drugs, such as nonsteroidal antiinflammatory agents, tricyclic
antidepressants, corticosteroids, benzodiazepines, amphetamines,
antiemetics, oral local anesthetics and bisphosphonates have
been suggested to have adjuvant analgesic effects."
Dalal et al commented: "Studies with human subjects have
confirmed the enhancement of opioid analgesia by amphetamines
and, in addition, have demonstrated that psychostimulant drugs
produce a decrease in somnolence and an increase in general
cognitive abilities. The greater cognitive alertness, moreover,
allows the use of larger opioid doses, which can produce a
substantial increase in analgesia."
Reich et al observed: "amphetamines... have been rarely
used in the past, but have been recently introduced in the
palliative treatment in oncology. They have stimulating,
antidepressive and perhaps coanalgesic effects. They can
alleviate sleepiness related to opiates analgesics which are
given in chronic pain."
A study of female migraine patients found they were
significantly more likely than controls to be using amphetamine,
although the authors did not indicate whether this was
considered a causative factor or an attempt at self-medication.
Following a clinical study of cancer patients in Bristol, O’Neill
concluded: "Adjuvant analgesic drugs and non-drug measures
should be used whenever possible, and drugs should be chosen
that will not contribute to existing difficulties. The
appropriate use of psychostimulants has yet to be
established..."
A retrospective Swedish study suggested that nitrous oxide
analgesia during childbirth may contribute to amphetamine
addiction later in life.
Summary
It is well-established within the scientific literature that
amphetamine can provide an analgesic (pain killing) effect in
its own right, and enhance the analgesic effects of opiate
painkillers (e.g. morphine, codeine).
Recent developments in the treatment of the terminally ill
suggests amphetamines may have a role to play in the management
of severe pain as an adjunctive therapy, by enhancing the
effects of opiates. However, this role is limited in long-term
use by the high degree of tolerance and dependence which
frequently develops with prolonged stimulant use.
Opiates are likely to cause drowsiness, reduced alertness and
impaired cognitive function - effects which are reduced or
reversed by amphetamine. The risk of respiratory depression with
high doses of opiates is also reduced with amphetamine, allowing
larger doses pain-relief.
The analgesic role of stimulant drugs is thought to mimic the
effects during stress, where pain (e.g. from an injury) is not
experienced during crises such as armed combat or other
potentially life-threatening events (such effects are even
reported in sporting contests).
Amphetamine and Cannabis: No scientific studies have been found
investigating the extent to which the analgesic effects of
cannabis and amphetamine may be related, nor as to any
interactions between the combined effects of these drugs on
analgesia or pain thresholds (i.e. whether the combined effects
are synergistic, additive, neutral or antagonistic compared to
either drug alone). This is clearly an area where further
research is needed.
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