I hope this article will interest some on this board.  After all morphine
helped even after psychosurgery hadn't.

I would think that Anafranil's ability to induce {*filter*}'s would suggest that
it must have some sort of opiate like qualities, even if Novartis doesn't
comment on it.

A Possible New Treatment Approach to Obsessive-Compulsive Disorder

Dear Sir:

I would like to report on a possible new treatment approach to
obsessive-compulsive disorder (OCD). The use of narcotic antagonists and
agonists has been of great benefit in a small number of treatment-resistant
cases of OCD and OCD-spectrum disorders that have presented to the anxiety
disorders clinic where I work. Two cases will be briefly discussed and the
rationale for the use of narcotic agonists/antagonists also briefly reviewed.

Case I is a 55-year-old, divorced, unemployed female who had severe OCD since
early adolescence. Her main symptoms consisted of cleaning, checking, and
preoccupation with detail that resulted in extreme slowness. Her illness
waxed and waned but had become progressively worse over the years. Response
to the usual antiobsessional medication was minimal. Under the care of a
previous psychiatrist, she had received bilateral cingulotomies (he amputated
parts of her brain) with no benefit. Under my care for the last 6 years, the
patient showed no response to trials of all of the selective serotonin
reuptake inhibitors (SSRIs), alone or in combination, or to a course of
intravenous clomipramine infusions.  Electroconvulsive therapy relieved her
comorbid depression only for a short period of time.  Cognitive-behavioural
therapy provided by an experienced behavioural therapist was of limited
benefit . A further psychosurgical procedure of bilateral anterior
capsulotomy provided only temporary modification of symptoms.

Over the last 2 years she developed a new symptom of compulsive picking that
has become so severe that on admission to hospital, her face, {*filter*}s, and
abdomen were severely excoriated.

Demoralized, with few remaining family supports, she was being assessed for a
nursing home placement because she no longer was able to cope on her own. On
the basis of reports in the veterinary literature of narcotic  antagonists
being effective in compulsive behaviours in animals, as well as on the proven
 safety of naltrexone in the treatment of drug and {*filter*} {*filter*}ion, I
decided to try this approach in this patient. Naltrexone 50 mg/day was given
initially and then increased to 100 mg/day. Within a few days, the compulsive
picking dramatically decreased, although the patient continued to be very
dysphoric. At this point, based on anecdotal report from another patient with
severe OCD that her symptoms had dramatically remissed for up to a week when
given morphine following surgery, I elected to try a narcotic agonist in this
particular case.

After a suitable washout period for the naltrexone, morphine sulphate was
given subcutaneously a dose of 10 mg . The response was dramatic. Twenty-four
hours later, the patient remained mildly euphoric and free of all OCD
symptoms. This state lasted for several days. {*filter*}morphine was then tried,
and after some adjustment, a dose of 30 mg was found to be effective for 6 to
7 days, particularly diminishing the compulsive picking and the dysphoria.
Other narcotic agonists such as propoxyphene and pentazocine, had no effect.

The patient continued to do well on the {*filter*}morphine and entered a
rehabilitation program, where the morphine was discontinued. She suffered a
relapse, but now she remains much improved after the morphine was restarted
at a dose of 30 mg every 5 to 6 days.

Case 2 was a 35-year-old single female who was unemployed but trained as an
accountant. She had severe trichotillomania, (compulsively plucked on her
hair) which began in her early 20s; she had received extensive treatment for
this condition, but all of the SSRIs including clomipramine, had been
ineffective. She had no other symptoms of OCD or depression.

The trichotillomania worsened under stress and was confined to her head and
eyebrows.  She wore a wig because of large areas of baldness.  Her life had
become very restricted because of the time spent in hair-pulling activity and
the embarrassment of her being bald.

Repeated trials of SSRIs with augmentation remained ineffective. A trial of
naltrexone was undertaken at 100 mg/day. After 2 to 3 weeks, the
trichotillomania dramatically decreased, and her hair started growing back.
Unfortunately she could not afford the cost of the medication and discontinued
it with a return of symptoms.

Since these 2 cases were treated, 4 other end-stage cases of OCD (the only
other option was psychosurgery) have been successfully treated with {*filter*}
morphine, the dose ranging from 20 to 40 mg given every 5 to 8 days. Three
cases of OCD-spectrum disorder (2 with trichotillomania, one with compulsive
{*filter*}) have been treated with naltrexone with marked improvement.

The use of narcotic antagonists has been undertaken before for various
impulse-control disorders in humans, as well as for stereotypical behaviour in
animals.

Repetitive, self-injurious behaviour in humans is a complex phenomenon to
understand and to treat. Narcotic antagonists such as naltrexone or naloxone
have been shown to diminish such behaviours in humans for several days
following the administration of a single dose. This approach has been tried
in mentally challenged {*filter*}s who repeatedly injure themselves and in
compulsive wrist cutters (1-4).

A similar positive effect is seen in stereotypical behaviours in animals such
as acral{*filter*}, flank sucking, tail chasing in dogs, crib biting, flank biting
in horses, and repetitive chewing behaviours in pigs, to name a few. In
animals, narcotic antagonists such as naltrexone, Nalmefene, and naloxone
have been effective for several days after a single dose (5-8).

The narcotic antagonist naltrexone has also been successfully used for the
treatment of {*filter*} and drug {*filter*}ion (9,10), although its mechanism of
action is not clear. It is postulated that the opiate receptor system
functions as part of the positive reinforcement or reward system of the
brain. Painful stimulation has been demonstrated to produce an increase of
endorphin release leading to pain relief. A model has been developed in which
pain-inducing behavior such as wrist cutting ispostulated to result in
endorphin release leading to relief of pain and tension, whichthen reinforces
the original behaviours (1,11).

In {*filter*}ism, narcotic antagonists are postulated to block this pleasure or
reward system, which leads to cessation of the drinking behaviour (12).

The opioid receptor system in the brain is complex, and although some of the
effects of morphine have been known for hundreds of years, it was only in
1973 that opiate-binding sites were discovered in the central nervous system
of mammals and not until 1976 that the firstendogenous opioids were
discovered (13,14).  Further to this, several classes of opiate receptors
have been delineated, the main ones being mu, delta, and kappa, although
there are others (15). Morphine works primarily on the mu receptor with
analgesia and/or euphoria being the result, but it has an effect on the other
receptors as well.

Subtypes of each receptor have also been identified, and of possible
relevance to OCD is the concentration of opioid receptors found in the
striatal system, particularly the caudate nuclei (16,17), which appear to be
an important region in the pathogenesis of OCD (18,19).

In the cases in which morphine was useful, it is puzzling why the effect
lasted for at least 5 days following a single {*filter*}dose. None of the patients
reported a euphoric response beyond what could be expected as a result of
symptom relief. This suggests the involvement of opioid receptors other than
the mu receptor. The risk of {*filter*}ion, if this is true, should be very low,
if it exists at all. The cases discussed are being followed very closely from
this perspective, but there has been no evidence of dose escalation.

The response to narcotic agonists or antagonists in a few cases is similar to
that reported in the veterinary literature and reinforces the concept of a
neuroethological approach to the understanding of OCD, with a possible common
pathogenesis for stereotypies in animals, such as the acral{*filter*} syndrome in
dogs, and similar repetitive motor behaviours in humans, such as compulsive
picking or hair pulling (20,21).

Although there are many useful treatment approaches for OCD, about 30% of
patients do not respond to traditional therapy and continue to remain very
chronically ill. The last-resort treatment is often psychosurgery, a procedure
not readily available for most (22).

It is hoped that this letter may stimulate other thoughts on this subject.
Clearly, there is a need for research. Of interest, a recent television
documentary on medical advances had a short section in OCD.  A psychiatrist
from Baylor Medical College in Texas was interviewedand made a brief comment
about the successful use of morphine in a few cases of otherwiseintractable
OCD.  I am in the process of trying to find the name of this individual.

              Lorne Warneke, BSc, MD, FRCPC
              Edmonton, Alberta
              References

              1. Richardson IS. Zaleski W. Naloxone and
              self-{*filter*}. Biol Psychiatry
              1983:18:99-101.
              2. Hennan B. et al. Naltrexone decreases
              self-injurious behaviour. Ann Neurol
              1987:22:550-2.
              3. Davidson W, et al. Effects of naloxone on
              self-injurious behaviour. Research in Mental
              Retardation 1993:4;1-4.
              4. Lienemann J, I Walter F. Reversal or
              self-abusive behaviour with naltrexone
              (letter].
              J Clin Psychopharmacol 1989:9:448-9.
              5. Kiley-Worthington M.
...

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As an OCD patient, this sounds promising but I am particularly concerned
with this statement

I would imagine taking a narcotic for an extended period of time would
result in {*filter*}ion and tolerance to the drug. Why do they claim the risk to
be low?

Ida

I have read that opiates are effective 30-40% of the time and that SSRIs are
effective anywhere from 50-80% of the time. {*filter*}e is used in England as a
pain killer and it is much more effective and cheaper than what we use on
cancer patients in the USA. From what I have read, as long as the person
does not experience the euphoria of an opiate, risk of {*filter*}ion is very
low. In other words, it is the euphoria that creates the addition. Oddly,
gamblers, runners and other non drug activities can also produce {*filter*}ive
behavior. We do produce these opiate like {*filter*} in our systems. I took
Valium, an {*filter*}ive drug, for 25 years without becoming {*filter*}ed to it
because I only took enough when I needed it for anxiety. Sometimes I took it
every day, then there were times I would not need it for months on end. I
have little doubt that opiates do work since I have tried them in the past
and they certainly do "clear" things up if you don't take too much.

--
Take care of your "self".

whatatrip

My therapist (used to be the head of a general psychiatric unit at McLean but
now in private practice) says he's used morphine for refractory depression
before and it worked, with no dosage creep, and I know of a couple other
psychiatrists who have done the same. (I'm sort of curious why morphine and not
methadone or LAAM, myself.) Some researchers are currently looking at a number
of mixed agonist/antagonists such as butorphanol, tramadol (also a 5-HT and NE
uptake inhibitor, so particularly promising), and buprenorphine. I hadn't heard
of anti-obsessive effects of opioids before, but it doesn't surprise me; OCD
is, at its heart, an anxiety disorder.

I'm sure a polite inquiry on alt.support.chronic-pain would give you an idea as
to whether people who take opiates for chronic pain have trouble quitting them.
I wouldn't think so, as long as the medication wasn't discontinued abruptly but
was tapered (just like any medication ought to be). "{*filter*}ion" and
physiological dependence aren't the same at all. (I actually dislike the word
"{*filter*}ion" because it's so loaded; I prefer to refer to DSM-IV "substance
dependence.")

-elizabeth

     Thankyou for posting this. I got a good laugh out of it. {*filter*} definitely
work, they're great!!! Cure my OCD. They'll cure everything until you get
{*filter*}ed, then it's not gonna be the OCD you're gonna worry about. Sure,
everything is safe in moderation but morphene could only be administered under
close supervision in a hospital cause giving someone a ready supply of the stuff
is incredibly dangerous, especially if they're being tortured 24 hours a day with
OCD and they're having a really bad day. If someone is so bad they're picking
pieces out of their body you would try anything but this aint no cure, not unless
you're in hospital and nothing else has worked. I prefer to fight this thing the
traditional way.
...

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Cole is involved in the research I mentioned, yes. They're all members of Club
McLean (psychiatry in Boston is an {*filter*}uous sport - is that metaphor mixed
enough for you?).

-elizabeth

Morphine's risk of {*filter*}ion isn't very low.
I think only very pathological cases should be treated with morphine.
Cases were the side effects of the drug would be preferable to those
of the morbid OCD.

This person is also legitimating morphine treatment based only in two
circumstancial cases. What about longer follow ups?

Cat Chow

With all respects this statment makes me laugh!
Of course we will always find freaks in nature.
Rasputin's killers had to finally stabb the guy because he wasn't
dying of the loadshit of poisin they put in his food!!!

But you and me and everybody in this NG would have probably died with
a tenth of that poisin.

Please, common sense is not a given. Cientist are not blessed with it
just because they're cientists and they can believe and say BS like
anybody else.
Cat Chow