ChapterPDF Available

Detoxification of Drug and Substance Abuse

Authors:

Abstract

Detoxification is a process of abolishing a substance of dependence from the body in a way which does not hinder the body’s physiology. Detoxification often takes a couple of days and half a month to finish, which is contingent upon the substance being abused, the seriousness of reliance and the help accessible to the client. Metabolism plays an important role in an effective detoxification process; some of the eminent enzymes are discussed in this review, which helps in excretion of xenobiotics. Psychosocial treatments nearby pharmacological medicines are fundamental to improve result. The over reliance conditions considered in this review are detoxification from opioids with clonidine-naltrexone, buprenorphine and other procedures, detoxification of benzodiazepines through adjunctive therapies and medications. Detoxification of psychostimulants with propranolol and amantadine is also discussed in detail.
Selection of our books indexed in the Book Citation Index
in Web of Science™ Core Collection (BKCI)
Interested in publishing with us?
Contact book.department@intechopen.com
Numbers displayed above are based on latest data collected.
For more information visit www.intechopen.com
Open access books available
Countries delivered to Contributors from top 500 universities
International authors and editor s
Our authors are among the
most cited scientists
Downloads
We are IntechOpen,
the world’s leading publisher of
Open Access books
Built by scientists, for scientists
12.2%
121,000
135M
TOP 1%
154
4,700
Chapter
Detoxification of Drug and
Substance Abuse
Sreemoy KantiDas
Abstract
Detoxification is a process of abolishing a substance of dependence from the
body in a way which does not hinder the body’s physiology. Detoxification often
takes a couple of days and half a month to finish, which is contingent upon the sub-
stance being abused, the seriousness of reliance and the help accessible to the client.
Metabolism plays an important role in an effective detoxification process; some
of the eminent enzymes are discussed in this review, which helps in excretion of
xenobiotics. Psychosocial treatments nearby pharmacological medicines are funda-
mental to improve result. The over reliance conditions considered in this review are
detoxification from opioids with clonidine-naltrexone, buprenorphine and other
procedures, detoxification of benzodiazepines through adjunctive therapies and
medications. Detoxification of psychostimulants with propranolol and amantadine
is also discussed in detail.
Keywords: opioids, cannabis, amphetamine, detoxification
. Introduction
Detoxification is the process of disengaging a person from a specific psychoac-
tive substance in a safe and effective manner. The choice of which strategy to use
for detoxification can depend on many factors, involving clinical judgment, the
user’s personal preference and circumstances, lifestyle and expectations, degree of
dependence and concomitant health problems. Detoxification does not imply that
a patient has been given the diagnosis of substance use disorder such as addiction,
abuse, or misuse of medications. Although addiction may necessitate detoxifica-
tion in order to begin drug rehabilitation treatment, there are many reasons that
patients must undergo detoxification. Detoxification refers to a decrease in biologi-
cal activity of a drug after it has been metabolized in the body. Biotransformation
is a critically essential pathway for drug detoxification and elimination in humans.
Biotransformation of drugs leads to termination or alteration of their biologic
activity, otherwise most drugs would have a prolonged duration of action. Despite
the fact that probably every organ in the human body is capable of metabolizing
drugs but the liver and small intestine serves as the dominant sites of expression of
the major drug metabolizing enzymes. Broad spectrums of enzymes are present in a
human that can catalyze biotransformation reactions, and they have been classified
precisely into Phase I and Phase II processes. Whereas Phase I represents oxidation,
reduction, and hydrolytic reactions, Phase II involves conjugation of the drug with
an endogenous molecule that generally increases the hydrophilicity of the adducted
Medical Toxicology
metabolite. Ultimately, all drug metabolites are excreted primarily through the
urine or bile. Many endogenous and Xenobiotics are lipophilic. They can easily cross
lipid bilayers & transported by lipoproteins. Metabolism of endogenous com-
pounds and xenobiotics allows organisms to convert lipophilic compounds to more
water soluble forms which facilitate excretion. Many xenobiotic compounds contain
aromatic rings and heterocyclic ring structures that we are unable to degrade or
recycle because those are structures are hydrophobic in nature.
. Detoxification as specific from substance abuse treatment
Detoxification is a lot of intercessions planned for overseeing intense inebria-
tion and withdrawal. Directed detoxification may forestall conceivably hazardous
complexities that may show up if the patient was left untreated. Simultaneously,
detoxification is a type of palliative consideration (diminishing the force of a tur-
moil) for the individuals who need to get abstinent or who must watch obligatory
forbearance because of hospitalization or legitimate contribution. At long last, for
certain patients it speaks to a point of first contact with the treatment framework
and the initial step to recuperation. Treatment/restoration, then again, includes a
group of stars of continuous remedial administrations at last proposed to advance
recuperation for substance misuse patients.
The accord board based on existing meanings of detoxification as an expansive
procedure with three fundamental segments that may happen simultaneously or as
a progression of steps:
Assessment involves testing for the nearness of substances of maltreatment
in the circulation system, estimating their focus, and screening for co-happening
mental and physical conditions. Assessment additionally incorporates an exhaustive
evaluation of the patient’s medicinal and mental conditions and social circumstance
to help decide the proper degree of treatment following detoxification. Basically,
the assessment fills in as the reason for the underlying substance misuse treatment
plan once the patient has been pulled back effectively.
Adjustment incorporates the medicinal and psychosocial procedures of help-
ing the patient through intense inebriation and withdrawal to the achievement of
a therapeutically steady, completely upheld, sans substance state. This frequently
is finished with the help of prescriptions, however in certain ways to deal with
detoxification no drug is utilized. Adjustment incorporates acclimating patients
with what’s in store in the treatment milieu and their job in treatment and recupera-
tion. During this time experts likewise look for the inclusion of the patient’s family,
bosses, and other huge individuals when fitting and with arrival of classification.
Cultivating the patient’s entrance into treatment includes setting up the patient for
section into substance misuse treatment by focusing on the significance of finish-
ing the total substance misuse treatment continuum of care. For patients who have
exhibited an example of finishing detoxification administrations and afterward
neglecting to participate in substance misuse treatment, a composed treatment
agreement may energize entrance into a continuum of substance misuse treatment
and care. This agreement, which is not legitimately official, is intentionally marked
by patients when they are steady enough to do as such toward the start of treatment.
In it, the patient consents to take an interest in a proceeding with care plan, with
subtleties and contacts built up before the completion of detoxification.
The cytochrome P450 (CYP) catalysts are otherwise called microsomal blended
capacity oxidases. The CYP compounds are layer bound proteins, present in the
smooth endoplasmic reticulum of liver and different tissues. They are the most
significant chemicals for Phase I biotransformation of medications. These catalysts
contain a heme prosthetic gathering, where heme gathering is the iron-porphyrin
Detoxification of Drug and Substance Abuse
DOI: hp://dx.doi.org/10.5772/intechopen.90380
unit. The oxidizing site in these chemicals is the heme focus, and is liable for the
oxidation of hydrophobic mixes to hydrophilic or progressively polar metabolites
for resulting discharge.
There are in excess of 300 distinctive CYP catalysts, which have been assembled
into a few families and subfamilies dependent on the amino-corrosive arrangement.
Out of these, 18 CYP families have been distinguished in warm blooded creatures,
containing significantly of families CYP1, CYP2 and CYP3. Some of the CYP
enzymes and their respective drugs are given in Table .
. Detoxification of opioid poisoning
This section sets out the key aspects of the pharmacology of the opioids and
other drugs used in detoxification, including the use of opioid agonists, partial ago-
nists and opioid antagonists. The point of detoxification for a ward narcotic client
is to kill the impacts of narcotic medications in a sheltered and viable way. Fitting
organization of pharmacological operators assumes a significant job in improving
the probability of a fruitful detoxification, while limiting the distress of withdrawal
experienced by the administration client.
. Opioid agonists
All narcotics, including heroin and methadone, are agonists that animate nar-
cotic receptors. Numerous narcotic agonists are additionally endorsed for their pain
relieving properties in torment the board, including morphine, codeine, dihydroco-
deine, oxycodone, hydrocodone and fentanyl.
2.1.1 Partial agonists
Buprenorphine is a partial agonist at the narcotic receptor subtype, which
implies that the framework is not completely animated in any event, when every
one of the receptors are involved. This lesser impact is the primary contributory
system hidden buprenorphine’s better wellbeing profile when taken alone, since the
edge for respiratory wretchedness is not come to in any event, when every one of
the receptors are involved. As a fractional agonist, buprenorphine can likewise seem
to go about as a rival (and all things considered may have been portrayed in more
seasoned writing as a blended agonist-rival). In the event that buprenorphine is
given to an individual who has taken a full agonist (for instance, heroin or metha-
done), it uproots the full agonist, because of buprenorphines higher proclivity at
the narcotic receptor, however just incompletely animates these receptors.
S. No. CYP enzyme Drug metabolized
11A2 Amitriptyline, clozapine
22A6 Acetaminophen, amodiaquine
32C8 Paclitaxel
42C9 Diclofenac, ibuprofen, phenytoin
53A4 Carbamazepine, erythromycin, zolpidem
62E1 Enflurane, halothane
Table 1.
List of drugs metabolized by various families of CYP enzymes.
Medical Toxicology
2.1.2 Antagonists
An antagonist, for example, naltrexone or naloxone, ties to the receptor yet
does not invigorate it. Naltrexone and naloxone have a high fondness with narcotic
receptors, to such an extent that they will dislodge existing agonists and keep
further agonists from official to the receptors. Along these lines if an agonist is
available animating the receptor, for instance heroin or methadone, taking naltrex-
one or naloxone will stop this incitement, coming about in accelerated (sudden)
withdrawal. Thus, naloxone is usually utilized in crisis drug to switch narcotic
overdose, while the more drawn out acting naltrexone is recommended as an
upkeep treatment to anticipate detoxified administration clients from backsliding to
narcotic use.
. Clonidine-naltrexone detoxification
This technique joins a quick, hastened withdrawal by naltrexone delivering seri-
ous withdrawal manifestations, with high portions of clonidine and benzodiaze-
pines when the naltrexone to improve the side effects. While shortening withdrawal
to 2–3days, proof is missing of longer restraint or naltrexone maintenance [1].
2.2.1 Rapid opioid withdrawal under general anesthesia
In the course of the most recent a very long while there has been a lot of
progress understanding the atomic and cell premise of practices identified with
nicotine addiction, and this comprehension has prompted focused on tranquilize
disclosure prompting new therapeutics for smoking discontinuance, for example,
varenicline [2]. These advances show that basic investigations of the neurobiolog-
ical premise of medication misuse can build our insight into why people become
dependent and what drives continuous smoking, however can likewise prompt
novel techniques for mediation to assist individuals with stopping and remain
abstinent. The information that has been increased about the systems fundamen-
tal nicotine support has been applied to understanding different practices that
drive continuous smoking. Focusing on the multimodal reason for nicotine admis-
sion may in this way bring about progressively compelling medicines for smoking
suspension going ahead.
2.2.2 Clonidine
The antihypertensive, α2-adrenergic agonist medicate clonidine has been
utilized to encourage narcotic withdrawal in both inpatient and outpatient set-
tings for more than 25years. It works by official to α2 autoreceptors in the locus
coeruleus and smothering its hyperactivity during withdrawal. Portions of
0.4–1.2mg/day or higher decrease a considerable lot of the autonomic parts of
the narcotic withdrawal disorder, however side effects, for example, a sleeping
disorder, torpidity, muscle throbs, and fretfulness may not be sufficiently taken
care of. Contrasted and methadone-helped withdrawal, clonidine has progressively
symptoms, particularly hypotension, however is less inclined to prompt post-
withdrawal rebound [3, 4]. Dropouts are bound to happen ahead of schedule with
clonidine and later with methadone. In an investigation of heroin detoxification,
buprenorphine improved on maintenance, heroin use, and withdrawal seriousness
than the clonidine gathering. Since clonidine has gentle pain relieving impacts,
included absence of pain may not be required during the withdrawal time frame
for therapeutic narcotic addicts.
Detoxification of Drug and Substance Abuse
DOI: hp://dx.doi.org/10.5772/intechopen.90380
. Toxicity mechanism of opioids
There are 3 primary narcotic receptors: delta, kappa, and mu. They happen all
through the CNS yet especially in territories and tracts related with torment recog-
nition. Receptors are likewise situated in some tactile nerves, on pole cells, and in
certain cells of the GI tract.
Narcotic receptors are animated by endogenous endorphins, which for the most
part produce absence of pain and a feeling of prosperity. Narcotics are utilized
remedially, principally as analgesics. Narcotics fluctuate in their receptor move-
ment, and a few (e.g., buprenorphine) have consolidated agonist and foe activities.
Mixes with unadulterated rival action (e.g., naloxone, naltrexone) are accessible.
Exogenous narcotics can be taken by practically any course: orally, intravenously,
subcutaneously, rectally, through the nasal layers, or breathed in as smoke. Pinnacle
impacts are come to around 10min after IV infusion, 10–15min after nasal insuf-
flation, and 90–120min after oral ingestion, despite the fact that opportunity to top
impacts and length of impact shift extensively relying upon the particular medica-
tion. Synapse discharge from neurons is regularly gone before by depolarisation
of the nerve terminal and Ca++ section through voltage-touchy Ca++ channels.
Medications may hinder synapse discharge by an immediate impact on Ca++ chan-
nels to diminish Ca ++ passage, or by implication by expanding the outward K+cur-
rent, in this way shortening repolarisation time and the term of the activity potential.
Narcotics produce both of these impacts in light of the fact that narcotic receptors
are obviously coupled through G-proteins legitimately to K+ channels and voltage-
touchy Ca++ channels. Narcotics additionally collaborate with other intracellular
effector components, the most significant being the adenylate cyclase framework.
. Detoxification of nicotine
Nicotine poisonous quality is frequently dismissed as far as helpful methodology
regardless of most patients being smokers. The fundamental nicotine detoxification
medications are considered beneath, yet likewise, clonidine can be considered as
a second-line treatment. Tiagabine, baclofen, gabapentin, varenicline, mecamyla-
mine (a non-particular NAch receptor foe) and topiramate have all been appeared
in concentrates to effectively affect suspension.
Nicotine replacement treatment (NRT) ties to nicotine acetylcholinergic (NAch)
receptors in the focal sensory system in a portion subordinate way. This diminishes
the desire to smoke, withdrawal impacts and any reward from cigarettes if the client
should backslide. It likewise gives a less destructive and less fortifying strategy for
organization contrasted and smoking, and can improve end rates by 50–70%. The
routine for detoxification treatment should begin 2weeks before the end endeavor,
as this has been demonstrated to be more successful than beginning treatment upon
the arrival of suspension itself. NRT ought to be proceeded for at least 2 months,
or for whatever length of time that vital. There is some proof that mental help is
likewise valuable, as forbearance with NRT is higher on solution than when it is
bought over the counter [5]. The slowest technique for conveying NRT is through
transdermal patches. These come in differing portions, where higher dosages might
be progressively advantageous for exceptionally subordinate smokers. Adequacy
can be improved by utilizing patches related to a quicker conveyance technique.
Biting gum, in portions of 2 and 4mg, is a case of a quicker conveyance technique,
as are inhalers, oral showers, sublingual tablets and capsules. The quickest convey-
ance technique is by nasal splash, which can supplant about a large portion of the
blood nicotine levels of smoking inside 5–10min [6]. All things being equal, NRT
Medical Toxicology
does not give nicotine as productively as smoking and does not copy the conduct
ceremonies, which bargains its viability for cessation [7]. In the event that the client
keeps on smoking during NRT, they may experience symptoms of nicotine poison-
ous quality, for example, queasiness, stomach torment, loose bowels, wooziness and
palpitations, and mix-up these for nicotine withdrawal.
. Nicotine receptor partial agonists
Nicotine receptor partial agonists check nicotine withdrawal side effects (by
going about as an agonist) and lessen smoking fulfillment (by going about as an
opponent), and might be valuable for improving long haul end. Varenicline is a par-
ticular fractional agonist for the a4-b2-NAch receptor with a moderate fondness for
the 5-hydroxytryptamine-3 receptor. Cahill etal. [8] indicated varenicline improved
long haul end by two to three times contrasted and fake treatment or bupropion,
was as yet powerful at lower dosages which likewise decreased the symptoms of the
medication, (for example, sickness). The suggested portion is 1mg twice every day
for 12weeks, which is come to by continuously expanding the portion from 0.5mg
once day by day during the prior week smoking suspension starts. An additional
12weeks of dosing can be utilized as backslide anticipation. It is hazy if these medi-
cines are better than NRT and there have been unconfirmed connections between
these medications and despondency with self-destructive speculation [9].
. Toxicity mechanism of nicotine
Nicotine ties to nicotinic cholinergic receptors, coming about at first, by means
of activities on autonomic ganglia, in overwhelmingly thoughtful anxious incite-
ment. With higher portions, parasympathetic incitement and afterward ganglionic
and neuromuscular bar may happen. Direct impacts on the mind may likewise
bring about heaving and seizures. Extensive proof focuses to contribution of
oxidative stress (OS), receptive oxygen species, lipid peroxidation, DNA harm, and
advantageous impact of cancer prevention agents. Beforehand, a proposal was pro-
gressed for cooperation of iminium metabolites which may work, by means of elec-
tron transfer (ET) with redox cycling, to deliver radical elements. The conjugated
iminium usefulness is one of the less notable ET types. The cationic metabolites
emerge from a few courses, including oxidation of nicotine itself, and protonation
of myosmine which starts from nornicotine through demethylation of nicotine.
Decrease possibilities, which are in the range manageable to ET invivo, loan assur-
ance to the hypothetical structure. Another metabolic course involves hydrolysis of
nicotine iminium to an open-chain ketoamine that, thusly, experiences nitrosation
to shape a harmful nitrosamine. Thusly, the nitrosamine fills in as a DNA alkylator
which can likewise produce conjugated iminiums by assault on specific nitrogen of
DNA bases. During the previous 14years, the speculation has delighted in generous
help. Expanding proof focuses to a job for OS in danger by nicotine involving sig-
nificant body organs, including the lung, cardiovascular framework, focal sensory
system, liver, kidney, testicles, ovary, pancreas, and throat.
. Detoxification of psychostimulants
Cocaine exerts its effects by interfering with the reabsorption of brains natural
neurotransmitters such as dopamine. Cocaine makes chemical changes in the brain
that may take time to reverse. A safe and secure environment monitored around
the clock by staff members may provide the smoothest possible detox. Physically,
Detoxification of Drug and Substance Abuse
DOI: hp://dx.doi.org/10.5772/intechopen.90380
the body may need to stabilize. Cocaine suppresses appetite and may cause
unhealthy weight loss, for example. A balanced diet plan can help restore a healthy
body weight. Physical exercise is also beneficial during detox as it releases natural
endorphins as well as increases physical strength and stamina, boosting self-esteem
and confidence levels. Yoga and meditation have been proven to help reduce stress,
and increase energy and focus naturally. Propranolol for cocaine detoxification
is just more viable than fake treatment if the clients are follower to the medicine.
Amantadine and other dopamine receptor agonists were seen as not any more
powerful than placebo. [10, 11] GABA-ergic medications might be a superior course
of examination, as glutamate exhaustion is related with rehashed cocaine adminis-
tration [12]. For instance, progesterone, tiagabine, topiramate and gabapentin were
found to diminish cocaine use in clients with low withdrawal seriousness.
Modafinil builds histamine discharge by means of the orexinergic framework
and is a feeble monoamine re-take-up inhibitor. Modafinil may upgrade glutamate
and hinder GABA, and has been seen as better than fake treatment regarding higher
restraint levels [13]. It is thought to go about as an ‘agonist substitution, hindering
the dopamine transporter and, to a flimsier degree, the noradrenaline transporter,
expanding extracellular dopamine and noradrenaline. Studies show modafinil may
improve electrotonic coupling, whereby the associations over hole intersections
turned out to be progressively viable. For amphetamine detoxification, mirtazapine
and amineptine were seen as incapable. Anyway it very well may be inferred that
bupropion and modafinil might be useful as an extra to conduct treatments.
. Detoxification of cannabis
In detoxification for cannabis, anticonvulsants, for example, valproate semiso-
dium and antidepressants, for example, bupropion, fluoxetine, mirtazapine and
nefazodone have demonstrated little benefit [14, 15]. Yearnings are decreased, yet
peevishness, uneasiness and tiredness are expanded. A significant issue in can-
nabis withdrawal is trouble dozing and has indicated this might be reduced with
zolpidem. Examination into rimonabant, a cannabinoid receptor adversary, was
ended because of unfortunate reactions. Some guarantee for cannabis detoxifica-
tion has been appeared by oral tetrahydrocannabinol (THC or dronabinol) and
lithium carbonate. A portion of 30–90mgday by day of THC, especially when
joined with lofexidine, has been appeared to lessen withdrawal manifestations, rest
issues, uneasiness, longings and burdensome symptoms [16]. Dronabinol (δ-9-
tetrahydrocannabinol) and lithium carbonate have been demonstrated to be helpful
for reducing withdrawal [13]. Be that as it may, for unlawful medications including
stimulants, cannabis and joy (MDMA), psychosocial treatments, for example,
keyworking and possibility the executives remain the prescribed treatment. There is
as yet a job for the clinician in the checking and treating of any emotional wellness
issues, including psychosis, wretchedness or danger of suicide. Withdrawal mani-
festations from GHB and its forerunners (γ-butyrolactone, GBL and 1,4-butanediol,
1,4-CB) can incorporate serious neuropsychiatric issues and autonomic insecurity,
which might be perilous and require escalated care. Less extreme yet continuing
reactions incorporate a sleeping disorder, uneasiness and depression [17]. Ringer
and Collins report pharmacological techniques to treat this incorporate the utiliza-
tion of high portion benzodiazepines (for instance, 40–120mg of diazepam),
perhaps joined with baclofen or different narcotics like pentobarbital if there is
no reaction to benzodiazepines. SSRIs ought to in a perfect world be maintained a
strategic distance from in cocaine and amphetamine clients because of conceivable
serotonin disorder, in spite of the fact that they are regularly utilized.
Medical Toxicology
. Toxicity mechanism for cannabis
Cannabis inebriation is a disorder perceived in DSM-IV and ICD-10, with both
mental and conduct (rapture, unwinding, expanded craving, weakened memory
and focus), and physical (engine incoordination, tachycardia, orthostatic hypoten-
sion), indications. Inebriation is generally mellow and self-restricting, not requiring
pharmacological treatment. The most serious impacts (tension, alarm, psychosis)
are best treated symptomatically with a benzodiazepine or second-age (atypical)
antipsychotic prescription. No medicine is affirmed explicitly for treatment of
cannabis inebriation.
Concentrates with the particular CB1 receptor opponent/opposite agonist
rimonabant propose that CB1 receptors intercede a considerable lot of the intense
impacts of cannabis in people. In a twofold visually impaired, fake treatment
controlled investigation of 63 solid men with a background marked by cannabis
use, single oral portions of rimonabant delivered noteworthy portion ward bar of
the abstract inebriation and tachycardia brought about by smoking a functioning
(2.64% THC) or fake treatment (twofold visually impaired) cannabis cigarette
2hours after the fact. The 90-mg portion delivered about 40% decreases in
appraisals of “high” “stoned” and “tranquilize impact” (on 100-mm visual-
simple scales) and a 60% decrease in pulse. Rimonabant alone delivered no huge
physiological or mental impacts and did not influence top THC plasma focus or
its time course.
This example of discoveries proposes that the watched lessening of cannabis
impacts was explicitly due to CB1 receptor bar, and not to decrease in cerebrum
THC fixation or checking impacts of rimonabant. CB receptor adversaries, for
example, rimonabant may be valuable in treating intense cannabis inebriation, in
the way that the mu-narcotic receptor (mOR) foes naloxone and naltrexone are
utilized to treat sedative inebriation. Be that as it may, such meds are never again
accessible for clinical use. Rimonant and comparable CB1 receptor rivals were
pulled back from clinical advancement and use in view of mental reactions related
with their long haul use.
. Detoxification of benzodiazepine
Long haul endorsing of high portions of benzodiazepines (more than 30mg
of diazepam) can be destructive. Benzodiazepine reliance is normally treated in
optional consideration, however may display close by other medication reliance.
It is suggested that clients of methadone and benzodiazepines ought to experience
detoxification from benzodiazepines first. Anyway there is proof that narcotic/ben-
zodiazepine clients may have less withdrawal impacts if buprenorphine is utilized
for detoxification. Benzodiazepine reliance is not just by means of rehash solution.
They are additionally obtained and abused unlawfully and there might be some an
incentive insupport” endorsing for high portion illegal clients before withdrawal.
Solutions for benzodiazepines ought to be diminished gradually to the most
minimal portion to control the reliance. There is no proof that week-on week-off
(beat) dosing is successful. Reliance on high dosages may require authority treat-
ment however can have a quicker pace of decrease, for example, lessening portions
significantly more than about a month and a half, without a danger of seizures.
Decrease of high portion use to a remedial portion level might be a helpful restor-
ative goal in some needy clients. Medications, for example, zolpidem, or melatonin
might be useful for any subsequent a sleeping disorder. The DH Drug Misuse and
Detoxification of Drug and Substance Abuse
DOI: hp://dx.doi.org/10.5772/intechopen.90380
Dependence rules prescribe changing over all benzodiazepines to a proper portion
of diazepam, which has a long half-life, and afterward decreasing the portion by an
eighth at regular intervals. Phenobarbital can likewise be utilized along these lines.
Different methodologies incorporate changing to a nonbenzodiazepine anxiolytic,
or the solution of aide drugs, for example, antidepressants or anticonvulsants. For
instance, pregabalin at higher dosages of 225–900mg have been seen as powerful,
and an ongoing Cochrane survey recognized carbamazepine as a potential extra to
lessen withdrawal impacts. Flumazenil, the benzodiazepine enemy, additionally
shows guarantee when given by moderate imbuement, and has the bit of leeway
that both high and low portions can be detoxified similarly well, and patients feel
well after the detoxification.
Detoxification of benzodiazepines has different therapeutic regimes depending
on the patient’s condition. Some of the protocols are discussed below.
• Need to institute a excellent therapeutic relationship between the general
practitioner and the patient—the process of benzodiazepine weaning is often
interminable and benzodiazepine doses may need to be continually negotiated.
• Need to treat earnestly any clinically significant anxiety and depression with
appropriate pharmacological or non-pharmacological methods. This is so as
to diminish the degrees of nervousness and discouragement while the patient
keeps on getting his/her standard benzodiazepine portion. There will be cutoff
points to what can be accomplished at times in light of the fact that the ner-
vousness and gloom indications might be a sign of benzodiazepine reliance.
• Need to prescribe a dose of diazepam equivalent to their usual regime and
maintain this dose for 1 week. The dose of diazepam can then be reduced
by approximately 1015% at weekly intervals until withdrawal symptoms
develop. If withdrawal symptoms develop smaller decrements and longer
intervals between dose reductions may be necessary. It may be very difficult for
patients to discontinue the final few milligrams. Although complete cessation
is preferable, a single daily dose of 2mg diazepam is sometimes acceptable.
A few patients may turn out to be progressively upset with regards to step-wise
decrease and it might become clear that they have under evaluated their portion.
It is basic that the believing relationship is kept up and portions renegotiated by
seriousness of withdrawal.
. Adjunctive therapies and medications
During the withdrawal organize, adjunctive medications, for instance, schol-
arly social treatment (CBT), loosening up treatment and planning in pressure the
board have exhibited to be simply humbly effective. If downturn ascends dur-
ing the withdrawal organize, the patient should be eagerly watched for reckless
ideation. Stimulant treatment may ought to be considered. Mental interventions,
for instance, CBT may be completed to address the scholarly signs of melancholy.
Carbamazepine at a portion of 200–800mg every day during withdrawal might be
fruitful in averting benzodiazepine reuse despite the fact that it has no announced
impact on the seriousness of withdrawal indications. Propranolol may help
when substantial indications, for example, tremor and uneasiness are lessened.
Cyproheptadine 4mg daily is useful for rest unsettling influence or a sleeping
disorder which is a typical element during detoxification.
Medical Toxicology

.. Symptomatic relief
Symptomatic help is fundamental for some patients in benzodiazepine with-
drawal notwithstanding sedation, especially when muscle issues or gut manifesta-
tions are noticeable. Side effects ought to be treated on an as required premise, as
per the specific side effect complex. Metoclopramide is recommended orally or IM
at a portion of 10mg at regular intervals as required for sickness as well as spew-
ing. An acid neutralizer 15-20ml orally is allowed at regular intervals as required
for indigestion or heartburn. Propantheline 15mg orally is allowed like clockwork
as required for stomach issues. Kaolin blend 15–20ml orally is allowed at regular
intervals as required for the runs. Quinine sulfate 300mg orally is given twice day
by day as required for muscle spasms. In any case, overabundance quinine sulfate
is dangerous to the heart. Paracetamol 1g orally is given each 4–6hours as required
for cerebral pains and other minor torments. Increasingly extreme a throbbing
painfulness can be treated with nonsteroidal calming drugs (NSAIDS, for example,
Ibuprofen 400mg orally at regular intervals as required gave there is no history of
ulcers, gastritis or asthma. A cox-2 inhibitor, for example, Celecoxib is a suitable
elective where there is a contra-sign for vague NSAIDS.
. Mechanism of cellular toxicity of benzodiazepines
Benzodiazepines (BZD) are natural bases with a benzene ring and a seven part
diazepine moiety; different side chains decide the strength, length of activity,
metabolite movement, and pace of disposal for explicit operators. BZDs apply their
impact by means of tweak of the gamma-aminobutyric corrosive A (GABA-A)
receptor. Gamma-aminobutyric corrosive (GABA) is the boss inhibitory synapse of
the focal sensory system.
The GABA-A receptor is made out of five subunits (alpha, beta, and gamma)
orchestrated in different mixes. The organization of subunits decides the liking of
the different xenobiotics that quandary to the receptor. Benzodiazepines tie at the
interface of the alpha and gamma subunits and, when bound, lock the GABA-A
receptor into an adaptation that builds its partiality for GABA.BZDs do not
modify the amalgamation, discharge, or digestion of GABA yet rather potentiate
its inhibitory activities by increasing receptor authoritative. This coupling builds
the progression of chloride particles through the GABA particle channel, caus-
ing postsynaptic hyperpolarization and a diminished capacity to start an activity
potential. The low occurrence of respiratory sadness with orally ingested BZDs has
all the earmarks of being identified with the low thickness of restricting locales in
the brainstem respiratory focus.
. Detoxification from alcohol
Withdrawal from liquor may not require pharmacological mediation, if the
seriousness of reliance and withdrawal manifestations do not require it. In any
case, thiamine enhancements might be important to keep away from the Wernicke-
Korsakoff disorder. Those with liquor reliance will in general have a diminished
dimension of thiamine in their eating regimen and ethanol can upset thiamine stock-
piling and use. Notwithstanding the medicines sketched out beneath, it tends to be
contended that different medications have a job in detoxification, for example, nal-
trexone, nalmefene, acamprosate, baclofen and disulfiram, despite the fact that these
are progressively fit to backslide aversion [9]. Another treatment with a potential job
in liquor detoxification is the psychotropic pain relieving nitrous oxide (PAN), which

Detoxification of Drug and Substance Abuse
DOI: hp://dx.doi.org/10.5772/intechopen.90380
has been distinguished by a Cochrane survey for mellow to direct liquor withdrawal.
This may have a quick remedial impact with negligible sedation (Table).
. Alcohol toxicity
Alcohol is a lethal substance and its danger is identified with the amount and
term of alcohol utilization. It can affect each organ in the body. In the mind, in a
solitary drinking scene, expanding levels of liquor lead at first to incitement (expe-
rienced as joy), fervor and garrulity. At expanding fixations liquor creates sedation
prompting uproars of unwinding, afterwards to slurred discourse, instability, loss
of coordination, incontinence, trance state and eventually Alcohol reliance and
unsafe liquor use demise through liquor harming, because of the sedation of the
essential mind works on breathing and flow. The reliance delivering properties of
liquor have been examined widely over the most recent 20years. Liquor influences
a wide scope of synapse frameworks in the mind, prompting the highlights of liquor
reliance. The principle synapse frameworks influenced by liquor are gamma-amino-
butyric corrosive (GABA), glutamate, dopamine and narcotic. The activity of liquor
on GABA is like the impacts of different narcotics, for example, benzodiazepines
and is answerable for liquor’s calming and anxiolytic properties. Glutamate is a
major neurotransmitter responsible for brain stimulation, and alcohol affects gluta-
mate through its inhibitory action on N-methyl D-aspartate (NMDA)-type gluta-
mate receptors, producing amnesia (for example, blackouts) and sedation. Chronic
alcohol consumption leads to the development of tolerance through a process of
S. No. Substance of abuse Detoxification process
1Opioids (morphine) Clonidine-naltrexone detoxification, rapid opioid withdrawal under
general anesthesia
2Nicotine Nicotine replacement therapy (NRT); e.g., tiagabine, baclofen,
gabapentin, varenicline, mecamylamine.
3Benzodiazepine Flumazenil as an antidote.
4Cannabis Antagonist approach, e.g., rimonabant
5Alcohol Disulfiram
6Cocaine Bupropion
7Amphetamine Modafinil
Table 2.
Summary of detoxification process of different substance of abuse.
Figure 1.
Progression of liver disease in chronic alcoholism.
Medical Toxicology

neuroadaptation: receptors in the brain gradually adapt to the effects of alcohol,
to compensate for stimulation or sedation (Figure ). This is experienced by the
individual as the same amount of alcohol having less effect over time. This can lead
to individual increasing alcohol consumption to achieve the desired psychoactive
effects. The key neurotransmitters involved in tolerance are GABA and glutamate,
with chronic alcohol intake associated with reduced GABA inhibitory function an
increased NMDA-glutamatergic activity.
This GABA—glutamate unevenness is adequate within the sight of liquor, which
expands GABA and lessens NMDA-glutamate movement. Be that as it may, when the
liquor subordinate individual quits drinking, the irregularity between these synapse
frameworks brings about the cerebrum getting overactive following a couple of hours
prompting horrendous withdrawal manifestations, for example, uneasiness, perspir-
ing, longing for, seizures and mental trips. This can be hazardous in extreme cases and
requires critical medicinal treatment. Rehashed withdrawal is additionally thought to
S No Structure of Substance abuse Structure of drugs used in detoxification process
Table 3.
Molecular structure of substance abuse and drugs used in detoxification.

Detoxification of Drug and Substance Abuse
DOI: hp://dx.doi.org/10.5772/intechopen.90380
underlie the lethal impact of liquor on neurons, prompting subjective disability and
cerebrum harm. The impacts of liquor withdrawal can take up to between 3months
and 1year to completely recuperate from (alluded to as the extended withdrawal
disorder). That being said, the mind remains strangely delicate to liquor and, when
drinking is continued, resistance and withdrawal can return inside a couple of days
(known as restoration). This makes it amazingly hard for an individual who has cre-
ated liquor reliance to come back to supported moderate drinking (Table  ).
. Conclusion
Detoxification is not an end in itself, however a transitional state among reliance
and restraint or decreased use. It can give a chance to restraint as a major aspect of
the recuperation venture, yet for certain medications may build the danger of over-
dose and supported backslide. It is a harmony between the substance clients needs
and inclination, decision of medicine, strategies for organization, and the force of
key working and psychosocial programs. Proof has appeared pharmacological treat-
ment for substance abuse works; however that it should be joined with psychosocial
treatment. We should now ask how we can best tailor built up medicines to suit the
requirements of people in distinction conditions. Questions remain with respect
to examinations between medicines, mixes of medications and ideal treatment
regimens. Much consideration has been given to affirmed medicines, for example,
methadone decreasing for narcotic reliance and benzodiazepines for liquor reliance,
and more research is required into rising treatment potential outcomes, for exam-
ple, oxytocin and flumazenil. Different medications for abuse are less all around
inquired about, to some degree because of the administrative obstacles associated
with setting up investigations of substances of abuse and controlled medications.
Ebb and flow investigation into extra or elective medicines is not vigorous enough
for significant survey bodies, which mean suggestion, are difficult to accomplish.
The decision of which technique to use for detoxification can rely upon numerous
elements, including clinical judgment, the client’s close to home inclination and
conditions, way of life and desires, level of reliance and associative medical issues.
Clinicians may need to tailor pharmacological medicines, for instance, in connec-
tion to danger of overdose if detoxification treatment can be occupied for infusion,
or if there are any dangers to kids living with the client if the treatment can be
brought home. For viable treatment plans, clients ought to be associated with their
treatment decisions. The choice of medication for detoxification in case of opioid
poisoning is very important. Methadone or buprenorphine should be offered as the
first-line treatment in opioid detoxification.
It should take into account whether the service user is receiving maintenance
treatment with methadone or buprenorphine if so, opioid detoxification should
normally be started with the same medication. Lofexidine may be considered for
people who have made an informed and clinically appropriate decision not to use
methadone or buprenorphine for detoxification or who have made an informed
and clinically appropriate decision to detoxify within a short time period with mild
or uncertain dependence (including young people). Clonidine should not be used
routinely in opioid detoxification.
Dihydrocodeine should not be used routinely in opioid detoxification.
Dosage and duration of detoxification has a crucial role. When determining
the starting dose, duration and regimen (for example, linear or stepped) of opioid
detoxification, healthcare professionals, in severity of dependence (particular
caution should be exercised where there is uncertainty about dependence) stabil-
ity of the service user (including polydrug and alcohol use, and comorbid mental
Medical Toxicology

health problems), pharmacology of the chosen detoxification medication and any
adjunctive medication. The duration of opioid detoxification should normally be
up to 4weeks in an inpatient/residential setting and up to 12weeks in a community
setting. In the course of the most recent a very long while there has been a lot of
progress understanding the atomic and cell premise of practices identified with
nicotine addiction, and this comprehension has prompted focused on tranquilize
disclosure prompting new therapeutics for smoking discontinuance, for example,
varenicline. These advances show that basic investigations of the neurobiological
premise of medication misuse can build our insight into why people become depen-
dent and what drives continuous smoking, however can likewise prompt novel
techniques for mediation to assist individuals with stopping and remain abstinent.
The information that has been increased about the systems fundamental nicotine
support has been applied to understanding different practices that drive continu-
ous smoking. Focusing on the multimodal reason for nicotine admission may in
this way bring about progressively compelling medicines for smoking suspension
going ahead. Restraint of synapse discharge is viewed as the significant system
of activity liable for the clinical impacts of narcotics. By the by, notwithstanding
broad examination, comprehension of the cell activities of morphine and different
narcotics is inadequate. This is astounding for a gathering of medications with such
amazing impacts, and is an impression of the unpredictability of the instruments
associated with synapse discharge. Affirmation of current speculations with respect
to components of narcotic hindrance of synapse discharge must anticipate the use
of progressively refined methods. Ongoing progresses in the atomic science of
narcotic receptors guarantee critical propels in narcotic pharmacology and should
help disclosure of narcotics with increasingly specific activities.
Conflict of interest
The authors declare no conflict of interest.
Author details
Sreemoy KantiDas
Faculty of Pharmacy, Lincoln University College, Malaysia
*Address all correspondence to: sreemoy_das@yahoo.com
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms
of the Creative Commons Attribution License (http://creativecommons.org/licenses/
by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.

Detoxification of Drug and Substance Abuse
DOI: hp://dx.doi.org/10.5772/intechopen.90380
References
[1] Kleber HD.Pharmacologic
treatments for opioid dependence:
Detoxification and maintenance
options. Dialogues in Clinical
Neuroscience. 2007;(4):455
[2] Cucchia AT, Monnat M, Spagnoli J,
Ferrero F, Bertschy G.Ultra-rapid opiate
detoxification using deep sedation with
oral midazolam: Short and long-term
results. Drug and Alcohol Dependence.
1998;(3):243-250
[3] Kleber HD, Riordan CE,
Rounsaville B, Kosten T, Charney D,
Gaspari J, etal. Clonidine in outpatient
detoxification from methadone
maintenance. Archives of General
Psychiatry. 1985;(4):391-394
[4] Jasinski DR, Johnson RE,
Kocher TR.Clonidine in morphine
withdrawal: Differential effects on signs
and symptoms. Archives of General
Psychiatry. 1985;(11):1063-1066
[5] Lingford-Hughes AR, Welch S,
Peters L.Nutt D.BAP updated guidelines:
Evidence-based guidelines for the
pharmacological management of
substance abuse, harmful use, addiction
and comorbidity: Recommendations from
BAP.Journal of Psychopharmacology.
2012;(7):899-952
[6] Frishman WH.Smoking cessation
pharmacotherapy—Nicotine and
non-nicotine preparations. Preventive
Cardiology. 2007;:10-22
[7] Roll JM, Higgins ST.A within-subject
comparison of three different schedules
of reinforcement of drug abstinence
using cigarette smoking as an exemplar.
Drug and Alcohol Dependence.
2000;(1-2):103-109
[8] McGregor IS, Bowen MT.Breaking
the loop: Oxytocin as a potential
treatment for drug addiction. Hormones
and Behavior. 2012;(3):331-339
[9] Lingford-Hughes A, Welch S,
Nutt D. Evidence-based guidelines for
the pharmacological management
of substance misuse, addiction and
comorbidity: Recommendations
from the British Association for
Psychopharmacology. Journal of
Psychopharmacology. 2004;(3):293-335
[10] Kampman KM, Dackis C, Lynch KG,
Pettinati H, Tirado C, Gariti P, etal.
A double-blind, placebo-controlled
trial of amantadine, propranolol, and
their combination for the treatment of
cocaine dependence in patients with
severe cocaine withdrawal symptoms.
Drug and Alcohol Dependence.
2006;(2):129-137
[11] Minozzi S,Amato L,Pani PP,
Solimini R, Vecchi S, De
Crescenzo F, etal. Dopamine agonists
for the treatment of cocaine
dependence. Cochrane Database of
Systematic Reviews. 2015;(5). Available
from: https://doi.org/10.1002/14651858.
CD003352.pub4
[12] Keys AS, Mark GP,Emre N,
Meshul CK.Reduced glutamate
immunolabeling in the nucleus
accumbens following extended
withdrawal from self-administered
cocaine. Synapse. 1998;(4):393-401
[13] Bowen R,McIlwrick J,
Baetz M, Zhang X.Lithium
and marijuana withdrawal. The
Canadian Journal of Psychiatry.
2005;(4):240-241
[14] Haney M, Hart CL,Vosburg SK,
Comer SD, Reed SC, Cooper ZD, etal.
Effects of baclofen and mirtazapine
on a laboratory model of
marijuana withdrawal and relapse.
Psychopharmacology. 2010;(2):
233-244
[15] Zuardi AW, Crippa JAS,
Hallak JE.Cannabis sativa: The plant
Medical Toxicology

that can induce unwanted effects and
also treat them. Revista Brasileira de
Psiquiatria. 2010;:51-52
[16] Moreira FA, Crippa JAS.The
psychiatric side-effects of rimonabant.
Revista brasileira de psiquiatria.
2009;(2):145-153
[17] Lin S-K, Chen C-H, Pan
C-H.Venlafaxine for acute heroin
detoxification: A double-blind,
randomized, control trial. Journal
of Clinical Psychopharmacology.
2008;(2):189-194
... Pharmacotherapy or medication use is the mainstay treatment option for severe disorders. These medications play an important role in detoxifying, stabilizing abusers, and preventing relapse [15,17]. Pharmacotherapeutic attempts to treat this disorder and common overdosage seen with most agents have unraveled various medications with potential for use as counter agents, some of which have gotten FDA approval and are currently in use. ...
Article
Substance use disorders (SUDs) are a leading cause of death and other ill health effects in the United States and other countries in the world. Several approaches ranging from detoxification, behavioral therapy, and the use of antagonists or drugs with counter effects are currently being applied for its management. Amongst these, drug therapy is the mainstay for some drug abuse incidence, as is in place specifically for opioid abuse or alcohol dependence. The severity of the havocs observed with the SUDs has triggered constant interest in the discovery and development of novel medications as well as suitable or most appropriate methods for the delivery of these agents. The chronic need of such drugs in users warrants the need for their prolonged or sustained systemic availability. Further, the need to improve patient tolerance to medication, limit invasive drug use and overall treatment outcome are pertinent considerations for embracing sustained release designs for medications used in managing SUDs. This review aims to provide an overview on up-to-date advances made with regards to sustained delivery systems for the drugs for treatment of different types of SUDs such as opioid, alcohol, tobacco, cocaine, and cannabis use disorder. The clinical relevance, promises and the limitations of deployed sustained release approaches along with future opportunities are discussed.
Article
Full-text available
The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people.
Article
Full-text available
Only a small percentage of individuals seeking treatment for their marijuana use achieves sustained abstinence, suggesting more treatment options are needed. We investigated the effects of baclofen (study 1) and mirtazapine (study 2) in a human laboratory model of marijuana intoxication, withdrawal, and relapse. In study 1, daily marijuana smokers (n = 10), averaging 9.4 (+/-3.9) marijuana cigarettes/day, were maintained on placebo and each baclofen dose (60, 90 mg/day) for 16 days. In study 2, daily marijuana smokers (n = 11), averaging 11.9 (+/-5.3) marijuana cigarettes/day, were maintained on placebo and mirtazapine (30 mg/day) for 14 days each. Medication administration began outpatient prior to each 8-day inpatient phase. On the first inpatient day of each medication condition, participants smoked active marijuana (study 1: 3.3% THC; study 2: 6.2% THC). For the next 3 days, they could self-administer placebo marijuana (abstinence phase), followed by 4 days in which they could self-administer active marijuana (relapse phase); participants paid for self-administered marijuana using study earnings. In study 1, during active marijuana smoking, baclofen dose-dependently decreased craving for tobacco and marijuana, but had little effect on mood during abstinence and did not decrease relapse. Baclofen also worsened cognitive performance regardless of marijuana condition. In study 2, mirtazapine improved sleep during abstinence, and robustly increased food intake, but had no effect on withdrawal symptoms and did not decrease marijuana relapse. Overall, this human laboratory study did not find evidence to suggest that either baclofen or mirtazapine showed promise for the potential treatment of marijuana dependence.
Article
• Inpatient narcotic detoxification with clonidine hydrochloride has been used since 1978. Outpatient withdrawal, potentially more useful, has not been adequately studied. This report describes a double-blind random assignment of 49 methadone hydrochloride—maintained patients whose dose had been lowered to 20 mg. Twenty-five were detoxified using methadone at 1-mg decrements, 24 by abrupt substitution with clonidine. Approximately 40% of both groups achieved successful detoxification, with one third maintaining abstinence over the subsequent six months. The groups were also largely equivalent on withdrawal symptoms, but the clonidine group experienced symptoms in the first half of the study and the methadone group in the second half. Clonidine appears to be a safe and efficacious outpatient treatment for opiate withdrawal, although the results were less favorable than those obtained in open or inpatient studies.
Article
• Reports of an antiwithdrawal effect for clonidine hydrochloride in acute opioid withdrawal are inconsonant with experimental findings that other nonopioids are ineffective. In the present investigation the antiwithdrawal effects of clonidine, morphine sulfate, and placebo were compared in volunteer addicts whose dependence was maintained by 15 mg of morphine sulfate given subcutaneously four times daily. Clonidine was effective but had a differential effect on the signs and symptoms of morphine abstinence. Compared with morphine, clonidine was more effective in suppressing autonomic signs of abstinence but less effective in reducing subject-reported symptoms and discomfort. It is concluded that the perception of the clinical usefulness of clonidine depends on whether objective measures or subjects' reports are treated.
Article
In this experiment we compared three different schedules of reinforcement for promoting and sustaining short-term drug abstinence. For pragmatic reasons, cigarette smoking was studied as an exemplar of drug self-administration. The three schedules studied were a fixed magnitude of reinforcement for abstinence, a progressive increase in magnitude of reinforcement for abstinence with a reset contingency for drug use, and a progressive increase in magnitude of reinforcement for abstinence without a reset contingency. Eighteen cigarette smokers experienced the three schedules in a counterbalanced order. Each schedule was in effect for 5 consecutive days (M–F), during which time abstinence was reinforced according to the different schedules of reinforcement. The total amount of reinforcement (money) available was the same during each condition. The progressive magnitude with a reset schedule was more effective than the other two schedules in sustaining an initial period of abstinence. These results systematically replicate and extend those from prior studies demonstrating the efficacy of schedules incorporating a progressively increasing magnitude of reinforcement with a reset contingency for sustaining initial drug abstinence, and demonstrate the importance of the reset contingency to that effect.
Article
Drug use typically occurs within a social context, and social factors play an important role in the initiation, maintenance and recovery from addictions. There is now accumulating evidence of an interaction between the neural substrates of affiliative behavior and those of drug reward, with a role for brain oxytocin systems in modulating acute and long-term drug effects. Early research in this field indicated that exogenous oxytocin administration can prevent development of tolerance to ethanol and opiates, the induction of stereotyped, hyperactive behavior by stimulants, and the withdrawal symptoms associated with sudden abstinence from drugs and alcohol. Additionally, stimulation of endogenous oxytocin systems is a key neurochemical substrate underlying the prosocial and empathogenic effects of party drugs such as MDMA (Ecstasy) and GHB (Fantasy). Brain oxytocin systems exhibit profound neuroplasticity and undergo major neuroadaptations as a result of drug exposure. Many drugs, including cocaine, opiates, alcohol, cannabis, MDMA and GHB cause long-term changes in markers of oxytocin function and this may be linked to enduring deficits in social behavior that are commonly observed in laboratory animals repeatedly exposed to these drugs. Very recent preclinical studies have illustrated a remarkable ability of exogenously delivered oxytocin to inhibit stimulant and alcohol self-administration, to alter associated drug-induced changes in dopamine, glutamate and Fos expression in cortical and basal ganglia sites, and to prevent stress and priming-induced relapse to drug seeking. Oxytocin therefore has fascinating potential to reverse the corrosive effects of long-term drugs abuse on social behavior and to perhaps inoculate against future vulnerability to addictive disorders. The results of clinical studies examining intranasal oxytocin effects in humans with drug use disorders are eagerly awaited. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.
Article
Cigarette smokers tend to die prematurely from a number of diseases. Cigarette smoking is an important modifiable risk factor for cardiovascular morbidity and mortality. Despite the clear health benefits of smoking cessation, smokers usually find it difficult to stop and behavioral therapies often prove insufficient. Pharmacologic intervention may aid the process because of the addictive nature of nicotine. Nicotine replacement therapy, which is regarded as first-line therapy, was developed to overcome the symptoms of nicotine withdrawal that many patients find distressing. Different modes of administration include inhalation and buccal or transdermal absorption. The orally administered non-nicotine drugs varenicline and bupropion are also regarded as first-line treatments, either used alone or as an adjunct to nicotine replacement therapy. Second-line treatments include clonidine and nortriptyline. Other treatment strategies that have been examined include monoamine oxidase inhibitors and selective serotonin reuptake inhibitors; efficacy has yet to be proven definitively. A novel approach to treatment using the cannabinoid-1 receptor antagonist rimonabant is also under investigation.
Article
Reports of an antiwithdrawal effect for clonidine hydrochloride in acute opioid withdrawal are inconsonant with experimental findings that other nonopioids are ineffective. In the present investigation the antiwithdrawal effects of clonidine, morphine sulfate, and placebo were compared in volunteer addicts whose dependence was maintained by 15 mg of morphine sulfate given subcutaneously four times daily. Clonidine was effective but had a differential effect on the signs and symptoms of morphine abstinence. Compared with morphine, clonidine was more effective in suppressing autonomic signs of abstinence but less effective in reducing subject-reported symptoms and discomfort. It is concluded that the perception of the clinical usefulness of clonidine depends on whether objective measures or subjects' reports are treated.
Article
Inpatient narcotic detoxification with clonidine hydrochloride has been used since 1978. Outpatient withdrawal, potentially more useful, has not been adequately studied. This report describes a double-blind random assignment of 49 methadone hydrochloride-maintained patients whose dose had been lowered to 20 mg. Twenty-five were detoxified using methadone at 1-mg decrements, 24 by abrupt substitution with clonidine. Approximately 40% of both groups achieved successful detoxification, with one third maintaining abstinence over the subsequent six months. The groups were also largely equivalent on withdrawal symptoms, but the clonidine group experienced symptoms in the first half of the study and the methadone group in the second half. Clonidine appears to be a safe and efficacious outpatient treatment for opiate withdrawal, although the results were less favorable than those obtained in open or inpatient studies.