Brain Scans, Genes Provide Addiction Clues

Systemized knowledge and its applications.
Post Reply
User avatar
Joined:Sat Jun 10, 2006 7:00 pm
Brain Scans, Genes Provide Addiction Clues -

Post by maoshantemple » Fri Apr 13, 2007 4:16 am


Scientists using advanced brain imaging and genetic testing to probe
the physiological basis of addiction are gleaning new insights into
these disorders and how to treat them.

A symposium sponsored by Brookhaven National Laboratory (Upton, NY),
held in conjunction with the American Association for the Advancement
of Science's annual meeting in San Francisco in February, highlighted
several advances in addiction science made over the past year.
Researchers presented findings from brain imaging studies revealing
the importance of memory and drug-related cues in addiction, the role
of monoamine oxidase-inhibiting compounds in cigarette smoking, the
damage to inhibitory controls caused by methamphetamine use, as well
as results from studies suggesting that genomics could be used to
better tailor addiction therapies.

Craving Key

Dopamine, a neurotransmitter associated with pleasurable feelings,
plays an important role in reinforcing the use of addictive
substances. Many studies have demonstrated that addictive drugs
increase endogenous dopamine levels in the nucleus accumbens of the
brain. This phenomenon, which also occurs in the brain of someone
engaged in eating or other activities necessary for survival, is one
of the most powerful mechanisms driving behavior, explained Nora D.
Volkow, MD, director of the National Institute on Drug Abuse.

Harder to explain is another key component of addiction: the intense
craving or desire that addicted individuals experience when they are
exposed to drug-associated cues, such as persons with whom they used
the drug, places where they used the drugs, and drug paraphernalia.
Now, however, brain imaging techniques are giving scientists a window
on what happens in an individual's brain during craving.

To probe this response, Volkow and her colleagues at Brookhaven
National Laboratory used positron emission tomography (PET) scans to
obtain an indirect measurement of dopamine levels in the brains of 18
cocaine-addicted individuals under two conditions: while watching
videos of people buying and using cocaine and also while watching
videos featuring nature scenes (Volkow et al. J Neurosci. 2006;26:6583-6588).

To gauge dopamine levels, the scientists injected each individual
with a radiotracer that binds dopamine receptors in the brain and
used PET to measure the signal produced by the receptor-bound
radiotracers. Endogenous dopamine competes with the radiotracer to
bind dopamine receptors, so as the brain releases molecules of
endogenous dopamine and they bind to receptors, fewer molecules of
the radiotracer are able to bind, and the signal weakens.

When the individuals viewed the cocaine-related video, their dopamine
levels increased significantly compared with the levels released
while they watched nature videos. The scientists noted the effect
particularly in the ventral striatum, suggesting this region may play
a key role in drug craving. Levels of craving reported by the
participants also correlated with the levels of dopamine increase.
Similar increases in dopamine levels in the ventral striatum have
been documented in individuals exposed to food cues, suggesting that
addiction hijacks the same pathways that make eating rewarding.

Targeted Treatments

New research also suggests that it may soon be possible to use
genetics or other factors to target existing treatments to the
individuals who may benefit the most from them. One existing drug
that may be most effective when used in a targeted fashion is naltrexone.

The US Food and Drug Administration (FDA) approved oral naltrexone
for the treatment of heroin addiction in 1984. Naltrexone blocks
heroin from binding to opioid receptors and prevents individuals from
experiencing the high associated with heroin use. Currently, it is
used almost exclusively to treat physicians, nurses, and pharmacists
with opioid addictions, said Charles O'Brien, MD, PhD, director of
the Center for Studies of Addiction at the University of Pennsylvania
in Philadelphia, at the symposium. A variety of factors, such as the
need to take a daily pill and occasional adverse effects, such as
nausea, have limited its use. In June, the FDA approved a lower-dose
monthly injectable form of the drug. This formulation circumvents the
liver and prevents nausea, and it also offers the benefit of less
frequent administration.

The drug also has been used to treat alcoholism, but studies suggest
it is most effective in individuals who have a strong family history
of alcoholism, who experience euphoria when using alcohol, and who
experience strong cravings (Monterosso JR et al. Am J Addict.
2001;10:258-268). These findings suggest that there may be a genetic
basis for a patient's response to naltrexone.

Further evidence that some patients are predisposed to respond to
naltrexone treatment came from a 2003 study of 141 patients randomly
assigned to receive naltrexone (n = 82) or placebo (n = 59). The
study found that patients with a variant of the gene encoding the
u-opioid receptor were more likely to benefit from the drug (Oslin DW
et al. Neuropsychopharmacology. 2003;28:1546-1552). During 12 weeks
of treatment, patients with 1 or 2 copies of the Asp40 allele who
were treated with naltrexone had a significantly lower rate of
relapse or stayed abstinent longer if they did relapse than did those
with 2 copies of the Asn40 allele. A second group of scientists
reported at the American College of Neuropsychopharmacology meeting
in December that they had replicated these findings in patients
participating in the Combining Medications and Behavioral
Interventions (COMBINE) trial, O'Brien said.

The findings may have broader implications for physicians trying to
select the best treatments for their patients. "Once we begin to
correlate genotype with medication response, then physicians will be
able to do a much better job of selecting the right medication from
the beginning," O'Brien said.

Mood-Boosting Cigarettes

While much research on smoking has focused on the effects of
nicotine, cigarette smoke contains 4000 chemical compounds, some of
which also reinforce smoking behavior. This may explain why nicotine
replacement therapies are often ineffective alone. In particular,
some chemicals in cigarette smoke inhibit monoamine oxidase (MAO), an
enzyme that breaks down neurotransmitters. Such inhibition may
produce antidepressant effects, as MAO inhibitors are used to treat
depression, said Joanna Fowler, PhD, director of the Center for
Translational Neuroimaging at Brookhaven National Laboratory.

Using PET, Fowler and colleagues found that compared with controls,
smokers have 40% lower levels of MAO in their brains and 35% to 45%
lower levels in other organs, such as the heart, lungs, kidney, and
spleen (Fowler JS et al. Nature. 1996;379:733-736, Fowler JS et al.
Proc Natl Acad Sci U S A. 2003;100:11600-11605). "We don't know the
physiological implications, but we think it may account for the
increased rate of smoking in diseases like depression," Fowler said.

The lower MAO levels also may account for smokers' lower risk for
Parkinson disease. Fowler explained that when MAO breaks down
neurotransmitters, it creates hydrogen peroxide, a source of damaging
free radicals that may contribute to Parkinson disease; smokers with
lower levels of MAO may thus have lower levels of free radicals.

Other groups are conducting clinical trials to determine whether
certain MAO inhibitors may be useful in smoking cessation. A
preliminary 8-week randomized placebo-controlled trial of selegiline
hydrochloride showed promising results (George TP et al. Biol
Psychiatry. 2003;53:136-143). Nine of 20 patients randomly assigned
to receive selegiline hydrochloride were abstinent at 1 week vs only
3 of 20 patients given placebo, and 6 of the patients taking the drug
were abstinent during the last 4 weeks of the trial compared with 1
patient in the placebo group. The scientists are currently conducting
a larger trial, Fowler said.

Scientists have also recently isolated MAO-inhibiting chemicals in
tobacco smoke (Khalil AA et al. Bioorg Med Chem. 2006;14:3392-3398).
In this and previous studies, the scientists identified
MAO-inhibiting effects of terpene trans-trans-farnesol in the rat
brain and in human, baboon, monkey, dog, rat, and mouse livers. Such
studies may lead to the development of smoking cessation treatments
or neuroprotective agents.

Boosting Inhibition

Brain imaging studies also are providing evidence that
methamphetamine use may cause functional and structural deficits that
interfere with users' ability to control negative emotions.

Edythe D. London, PhD, of the Semel Institute of Neuroscience and
Biobehavioral Science at the University of California in Los Angeles,
and colleagues have used PET scans and radiolabeled glucose to
monitor and compare brain activity in methamphetamine-addicted
individuals who have abstained from the drug for 4 to 11 days with
that of controls (London ED et al. Arch Gen Psychiatry.
2004;61:73-84). They found abnormally low levels of activity (as
measured by glucose metabolism) in the cerebral cortex that was
related to symptoms of depression.

More recent findings by researchers from the University of California
in Los Angeles provide more evidence that individuals who use
methamphetamine lose the ability to control their negative emotional
responses. Using functional magnetic resonance imaging, the
scientists measured brain activity in methamphetamine-dependent
individuals and controls as they viewed emotionally charged images.
The methamphetamine-dependent individuals reported a weaker emotional
response to the images than did controls, but their scans revealed
more activity in the amygdala, a region involved in regulating
emotion. When asked to suppress their emotional response to the
images, healthy individuals showed activity in part of the prefrontal
cortex, but methamphetamine-dependent individuals did not.

London said the findings suggest that methamphetamine use leads to a
loss of function in parts of the brain that control emotion. This,
she said, may explain why methamphetamine users often are involved
with serious crimes and violence and why they have difficulty
abstaining. "It could be that they misinterpret environmental stimuli
and react in a strong way," she said.

She and her colleagues are now studying whether modafinil, a drug
used to treat narcolepsy, might help in treating methamphetamine
dependence. The drug has been shown to improve inhibitory control in
healthy individuals and in those with attention-deficit/hyperactivity
disorder. Such a means to control a problematic symptom of
methamphetamine abuse may improve the effectiveness of existing
therapies, such as behavioral therapy

Joined:Tue Jul 31, 2007 7:00 pm

Re: Brain Scans, Genes Provide Addiction Clues -

Post by barita_lola » Fri Aug 10, 2007 1:35 am

Well friend, I have recently gone through Heroin Addiction and at the moment am doing my "Rattle".I am concerned that i am going to relapse and fall back into it. I feel lost without it,like i have nothing to do.A lot of things annoy me without going into too much detail.It blocks out all of it. Can anyone give me advice.My doctor is no help at all

Joined:Wed Dec 06, 2006 7:00 pm

Re: Brain Scans, Genes Provide Addiction Clues -

Post by agni » Fri Aug 10, 2007 8:55 pm

barita_lola wrote:Well friend, I have recently gone through Heroin Addiction and at the moment am doing my "Rattle".I am concerned that i am going to relapse and fall back into it. I feel lost without it,like i have nothing to do.A lot of things annoy me without going into too much detail.It blocks out all of it. Can anyone give me advice.My doctor is no help at all
hang on friend
wish i could help, i am too uninformed

please look around here, search
there is lots of info that can help
look elsewhere too

if the doctor is no help
time for a new doctor
or someone you can trust

some people doctor themselves, successfully

good luck

Joined:Sat Feb 02, 2002 7:00 pm

Re: Brain Scans, Genes Provide Addiction Clues -

Post by BurningSnail » Mon Aug 13, 2007 2:24 am

Hey lola, maybe I can help. I have also had battles with opiate habits, which caused me many social problems as well as ulcers that were killing me back when I joined here. Now I realize the truth of addiction. Addiction is not dependence upon a compound. It is a whole system of socio-psychological control which has been engineered and directed at you by people seeking to control the entire world. sounds crazy right? When does the word addiction begin appearing in literature? What defines addiction?

I tell you this right now, addiction is a system by which you are given an excuse not to control yourself. With an excuse, you are no longer responsible for your actions, you dont have to work on any of your problems, because its the drug addiction causing them right?

Ibogaine is also a powerful tool. It legal status makes discussion hard in some countries, but it is worth looking into if you expect to be dopesick for an extended period of time, or if you feel your addiction is psychologically rooted, not pharmacological. I can't give you magical advice to make it all better for you, but I can give you hope. It can be done, hang on brother(or sister as it may be) you can do this. And don't expect help from a doctor, at least not in the US. These people are doing their jobs, which is keeping people coming back. talk about smack dealers. you ever noticed the man is always late? makes you wonder why filling a scrip takes two hours if its an opiate, huh? anyway im rambling. if you have specific questions, ask them in a post or PM me. we want to help, actually.

Joined:Fri Mar 25, 2016 5:50 am

Re: Brain Scans, Genes Provide Addiction Clues

Post by sage-borodin » Thu Jun 15, 2017 9:14 am

I was going to recommend ibogaine as well, which is prime for opioid treatment due to some pharmacological features of it, and it's metabolite, however the compound can also treat alcohol, cocaine and methamphetamine addiction.

Some ibogaine centers are even incorporating 5-meo-DMT into their treatment, where after one has recovered from the Ibogaine, the 5-meo-DMT is administered.

Around 10 years ago I suffered from mild depression as well as polysubstance abuse issues. I had been using psilocybin fungi heavily during thus time and by random chance, and out of pure curiosity I smoked DMT. I smoked an extreme extreme dose, and had what can be called a "peak experiance" or "shamanic crisis", and I have never been the same since.

Before this dmt event I was entangled in a toxic relationship with a women who was emotionally unstable, highly manipulative, extremely dishonest and nearly pathological in her constant lying and backbiting, she was horribly abusive, and an addict as well. After that first DMT event all personal attachment for her vanished, I was able to see her clearly without the blinding influence of emotion and attachments, as well as situation which she had created around me. So, I decided to leave her, which actually took months, she ended up destroying everything I owned, and spreading lies to all of our common associates, but I was free from the situation at last, and could finally progress in life. My next step was immediately stopping the use of all drugs aside from a select group of psychedelics and cannabis. This occurred nearly effortlessly, there was no "struggle with addiction", the changes had been made nearly instantaneously after I inhaled my first dose of dimethyltryptamine, and within a month after the first DMT event I was completely drug free. My view had been altered, there was nothing desirable left regarding these substances, and stopping their use was more than easy for me.

Then another change occured, I cut off contact with the majority of the people I would socialize with. I finally understood the deep impact of their influence, and how it was preventing my progress. I am a reclusive person, so this was not a challenge, it was just a matter of waiting until I could meet good hearted, well motivated individuals, who were positive in thought and action, and dedicated to honesty, compassion, and being the best person possible, people who would further my progress and who were sources of good karma. As they buddha (kind of) said:
If you cannot find a good companion to walk with, walk alone, like an elephant roaming the jungle. It is better to be alone than to be with those who will hinder your progress.

In reeality this is an amalgamation of two quotes:

329. If for company you cannot find a wise and prudent friend who leads a good life, then, like a king who leaves behind a conquered kingdom, or like a lone elephant in the elephant forest, you should go your way alone.

330. Better it is to live alone; there is no fellowship with a fool. Live alone and do no evil; be carefree like an elephant in the elephant forest. ... -progress/
Surely enough after a short period of keeping to myself I managed to locate such people. I only associate with a very small group of individuals, which works great in my situation, specially since I work with these individuals as well.

After the DMT event, I dove full force into my studies, I spent every minute of every day in my notebook, or textbook, or workspace. My studies and work still consume the majority of my time, but it's work that I love to do, it's work that I would be doing on my free time regardless. Fortunately my obsession with organic chemistry connected with my obsession with psychedelics in an incredibly fortunate manner.

Then the last major change was spirituality, I was agnostic before this DMT event, leaning towards atheism. I am still very scientifically oriented in thought, I am very skeptikal and always demand empirical evidence, however, during this event I experienced death, dismemberment, resurrection, and rebirth. I no longer had to believe in non-physical conscious existance which follows the death of the physical body, I had experienced it first hand. I always had an interest in eastern philosophy, however after this event it took on a new meaning, I could actual understand and take seriously spiritual concepts which I had either missed or dismissed prior. Buddhism, taoism, Hinduism, and shamanism began to have a much greater influence in my life.

I have not suffered from any type of depression or mental health issue, or suffered any issue relating to drug use since this DMT event.

Aside from all that I have been truly happy, not the type if happiness that is externally derived, but true happiness with spiritual balance. I no longer fear death, and have deep personal insight regarding it. If I lost everything I owned and was treated terribly by every human on earth it could not shake the happiness, joy, and love for life which I have attained, for this happiness comes from inner clarity, balance, and understanding.

Misc. Related research: ... urces-list
At the bottom of the list in the link above we find anecdotal evidence of cannabis and psilocybin treating bipolar.

Science shows that long term and permanent changes can be induced by use of these compounds.
these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation. These changes could underlie the previously reported personality changes in long-term users and highlight the involvement of the PCC in the effects of psychedelics.
Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
I feel that ibogaine, or even ayahuasca and LSD are for more likely to be effective than other methods of treatments.

I think the way that drugs, and drug users and drug use are viewed in modern society is absurd. I also feel nearly the same regarding the types of treatment which are offered, but this is another issue.

Post Reply