Amphetamine and Pain Relief
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.
References
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