Addiction

Post Two...

Now we return to the never ending research paper. All right, I have read far longer research paper than this one, but the use of citations is pretty significant in this one. It’s… a lot…

Materials and methods

Participants

These data were drawn from a National Institute on Drug Abuse (NIDA)-funded substance abuse treatment trial conducted at two adult correctional facilities in New Mexico. To be eligible, participants had to volunteer, meet DSM-IV (American Psychiatric Association, 1994) criteria for lifetime dependence on methamphetamine, heroin, or cocaine, and had to have used the drug within 3 months prior to their incarceration. Participants were given drug tests before each treatment session 2, but due to ethical considerations, were given the opportunity to continue treatment and study participation regardless of test results. Exclusion criteria included: estimated full-scale IQ less than 70, less than a sixth grade reading level, current antipsychotic medication use, psychotic disorder diagnosis for self or a first-degree relative, or past or current central nervous system disease. Five participants were excluded due to motion during scanning or poor image quality (e.g., deformations due to dental work). The final sample consisted of 137 individuals (mean age = 34.03, SD = 8.18; 93 females; see Table 1 for race/ethnicity). Participants gave written informed consent and were compensated $1 per hour, commensurate with the rate of pay for labor inside correctional facilities. Study materials and procedures were approved by the UNM HSC Institutional Review Board.

The DSMIV? All right…the DSM5 was out when this research paper was done, but okay, we can do a flashback I guess.

There are charts in the study, but you will have to link over to see them, as I cannot extract them. Maybe there is a way to do so, but I am not that dedicated.

Assessments

Psychopathy

Psychopathy was assessed using the Hare Psychopathy Checklist-Revised (Hare, 2003) (PCL-R). Trained researchers reviewed institutional records and conducted semi-structured interviews regarding participants’ psychosocial histories and interpersonal and emotional skills. Individuals are rated on a 3-point scale for 20 items, with scores ranging from 0 to 40. Traditional factor analyses of the PCL-R have revealed a two-factor structure (Harpur et al., 1989; Hare, 2003), although other models have been developed (Cooke and Michie, 2001), including a four facet model (Hare, 2003). Factor 1 (potential range: 0–16) comprises interpersonal (e.g., grandiosity, deceitfulness; Facet 1) and affective traits (e.g., lack of empathy, shallow affect; Facet 2), and Factor 2 (potential range: 0–20) comprises lifestyle behavioral (e.g., impulsivity, stimulation-seeking; Facet 3) and antisocial traits (e.g., poor behavioral controls, early behavioral problems; Facet 4). Interviews were videotaped to conduct reliability assessments. Double ratings were conducted on 16.8% of the sample, selected randomly. The intraclass correlation coefficient (ICC1one-way random effects model) was 0.83.

I mean… it’s not great to construct a cohort with the PCL-R, but they are following up with fMRI, so I suppose I cannot complain too much. I still do not like it though.

Substance use

Substance use was assessed in two ways:

Number of Substance Dependence Diagnoses. Trained researchers interviewed participants using the Structured Clinical Interview for DSM-IV disorders (First et al., 1997) (SCID) to assess lifetime dependence according to DSM-IV criteria. The total number of substances including alcohol for which an individual met lifetime dependence criteria was calculated (scale: 0–8).

Years of Regular Substance Use. A modified version of the Addiction Severity Index (McLellan et al., 1992) (ASI) was used to calculate the cumulative years of regular use (i.e., three or more times per week) for all substances (alcohol, heroin, cocaine, methamphetamine, cannabis, hallucinogens, and inhalants) combined. The ASI is a brief interview that asks details about the duration, frequency, and amount of use of multiple types of drugs.

Still with the DSMIV… So weird.

Other measures

Vocabulary and Matrix Reasoning subtests of the Wechsler Adult Intelligence Scale (Wechsler, 1997) were used to estimate the full-scale IQ (Ryan et al., 1999). The Wide Range Achievement Test Word Reading subtest (Wilkinson, 1993) (WRAT-3) was used to assess reading level. The SCID was used to assess past and current Axis I disorders. Individuals self-reported their primary drug of choice (i.e., methamphetamine, cocaine, or heroin). See Table 1 for descriptive statistics on demographic and study variables.

Stimuli and task

Imaging data were collected prior to the participants’ initiating the study’s 12-week treatment program. Two types of pictures (32 drug-related and 32 neutral) were selected from the popular media. Drug-related pictures depicted drugs or drug paraphernalia related to cocaine, heroin, and/or methamphetamine (e.g., white powder with a razor blade, a hand holding a syringe, a pipe). Neutral pictures depicted non-drug objects and scenes (e.g., white fluffy clouds, folded hands, a pen). Participants were instructed that they would see a series of pictures presented one at a time for 6 s. For each picture they were told to determine if anything in the picture gave them a craving feeling or desire to use drugs. Then they were instructed to rate their intensity of drug craving (in the form of a growing red bar) on a scale from 1 (no craving) to 5 (extreme craving) based on their immediate level of desire, not how they think they should feel or would hope to feel. After the rating screen, a black screen with a white fixation cross was presented for 4 s. Twenty null fixation trials the same duration as picture trials (i.e., picture + rating + fixation = 14 s) were interspersed randomly. Each participant completed two runs of 52 trials (16 drug-cues, 16 neutral, and 20 null fixation stimuli per run).

All right, my Significant Other just described the looking at drug related images creating a physiological response, such as people who love animals seeing a picture of a cat and having a reaction, which reinforces my thought that addiction and oxytocin are related.

Grok had this to say:

Yes, oxytocin (often called the “love hormone” or “bonding hormone”) plays a significant role in addiction, both in the underlying neurobiology of substance use disorders (SUD) and as a potential therapeutic target.

pmc.ncbi.nlm.nih.gov

How Oxytocin Interacts with Addiction

Oxytocin is a neuropeptide produced in the hypothalamus that influences:

• Social bonding and prosocial behavior

• Stress regulation (via the HPA axis)

• Reward processing (especially through interactions with dopamine in the mesolimbic pathway, including the nucleus accumbens and ventral tegmental area)

Addiction hijacks the brain’s natural reward system (dopamine surges from drugs/alcohol), while also dysregulating stress responses and social functioning. Chronic substance use often blunts the endogenous oxytocin system, leading to:

• Heightened stress and anxiety during withdrawal

• Reduced sensitivity to natural social rewards

• Increased vulnerability to cravings and relapse

Oxytocin counters these effects by:

• Modulating reward — It can dampen drug-induced dopamine release, reducing the reinforcing “high” from substances like alcohol, cocaine, methamphetamine, and opioids.

• Reducing stress and negative emotions — It helps normalize hyperactive stress responses and lowers withdrawal-related anxiety or dysphoria.

• Attenuating cravings — Especially cue-induced or stress-induced cravings.

• Promoting social salience — It may help restore interest in healthy social connections, which are often eroded in addiction.
  sponsored.chronicle.com

This involvement spans multiple stages of the addiction cycle (binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation).Evidence from Research

• Preclinical (animal) studies — Strong and consistent. Oxytocin administration (central, systemic, or intranasal) reduces self-administration, consumption, withdrawal symptoms, and reinstatement/relapse-like behavior for alcohol, opioids, cocaine, methamphetamine, and other drugs. For example, it blocks alcohol’s effects in the brain’s reward centers and prevents escalated drinking in dependent animals.
  scripps.edu

• Human studies and clinical trials — More mixed but promising. A 2023 systematic review of randomized placebo-controlled trials found oxytocin showed benefits across SUDs, with the most consistent effect being reduced withdrawal symptoms (especially after opioid cessation). It also reduced negative emotional states, general cravings, cue-induced cravings, and consumption in some trials. Effects were seen for alcohol, opioids, stimulants, and others, though not uniformly across all studies or participants.
  sciencedirect.com

Gender differences, trauma history, and individual factors (e.g., baseline oxytocin levels or attachment style) can influence outcomes. For instance, oxytocin may reduce cocaine cue-induced cravings and amygdala activity more reliably in certain subgroups (e.g., men with trauma history).Potential as a Treatment

Intranasal oxytocin (a non-invasive delivery method) is the most studied form. It is generally well-tolerated and already used in other contexts (e.g., labor induction). Researchers are exploring it as an adjunct to existing therapies for:

• Reducing acute withdrawal

• Lowering relapse risk

• Enhancing psychosocial interventions by boosting social engagement

Ongoing or recent trials have tested it for alcohol use disorder, opioid dependence, stimulant use, and co-occurring conditions like PTSD. Results are encouraging but not yet definitive—larger, well-powered trials are needed.

sciencedirect.com

Limitations and Caveats

• Oxytocin’s effects can be context-dependent (sometimes prosocial, sometimes not) and person-dependent.

• It does not “cure” addiction on its own; it is best viewed as a potential adjunct that targets specific mechanisms (reward dysregulation, stress, social deficits).

• Not all studies show benefits, and more research is required on optimal dosing, duration, and who benefits most.

In summary, oxytocin is deeply involved in the neurobiology of addiction—primarily by opposing the hijacking of reward and stress systems—and shows real promise as a novel treatment approach, especially for withdrawal, cravings, and supporting recovery through social reconnection.

That goes back to the rat example from the first post, and makes sense to me, as psychopaths lack the ability to process oxytocin, so whatever effects that it has on neurotypicals, psychopaths totally lack. Add that to the differences in the structure and function of the brain.

MRI data acquisition and statistical analysis

Participants were scanned on the Mind Research Network 1.5T Siemens Avanto mobile MRI, stationed at the correctional facilities, using an EPI gradient-echo pulse sequence (TR 2000 ms, TE 39 ms, flip angle 75°, FOV 24 × 24 cm, 64 × 64 matrix, 3.8 × 3.8 mm in-plane resolution, 4 mm slice thickness with 1 mm gap, 27 slices).

Data were preprocessed and analyzed using Statistical Parametric Mapping software (SPM5; http://www.fil.ion.ucl.ac.uk/spm). The ArtRepair Toolbox (Mazaika et al., 2009) was used to detect and remove severe image artifacts. ArtRepair-detected artifactual images were replaced and a regressor was created to remove the effects of the outliers in the statistical analyses. Following ArtRepair each run was realigned using INRIAlign, a motion-correction algorithm that is unbiased by local signal changes (Freire et al., 2002). The six realignment parameters (three translations and three rotations) and second-order movement parameters were entered as covariates in the statistical models below in order to remove variance due to movement. Realigned images were spatially normalized to the Montreal Neurological Institute (MNI) template and smoothed with an 8 mm full-width at half-maximum (FWHM) Gaussian smoothing kernel. Low frequency noise was removed using a high pass filter (cutoff: 1/128 s). Pictures (drug-related and neutral), ratings, and null fixation trials were modeled separately. Pictures were modeled with the standard SPM hemodynamic response function. For each participant, images that represented the hemodynamic response associated with viewing drug-related vs. neutral pictures were computed.

I am not a neuroscientist, so make of this what you will. Seems like a pretty standard scanning procedure.

One-sample t-tests in SPM5 were used to detect differences in viewing drug-related pictures vs. neutral pictures (i.e., main effects), and multiple regression analyses were used to evaluate the relationship between psychopathy and the neural associates of drug craving. PCL-R Total score was the predictor of most interest. PCL-R factors and facets were also examined to observe the unique variance accounted for by each factor or facet.

This is similar to the fMRI that I did. They use emotive and non-emotive images, and see where your brain lights up. Pretty typical.

After going through this paper, I don’t see a point in responding to the brain scan parts, as I can’t really add much to it. Instead, I think I will address the conclusions, and one serious problem that I find with their methodology/conclusions.

Conclusions

Numerous functional imaging studies have associated psychopathy with dysfunction in limbic and paralimbic regions, many of which have also been implicated in drug craving. This study found a negative association between psychopathy scores and engagement of craving-related areas during the viewing of drug cues. Abnormal activity in limbic and paralimbic areas in psychopathy has been demonstrated in multiple domains, including moral decision-making (Harenski et al., 2010), fear conditioning (Birbaumer et al., 2005), emotional memory (Kiehl et al., 2001), and now responses to drug cues. It will be important to follow up on the present line of work in order to develop more effective and efficient drug abuse treatments by considering an individual’s level of psychopathy when determining the most effective treatment strategy. This work has the potential to reduce the extreme burden—both financial and otherwise—of drug use disorders.

There you go. Psychopathy mitigates addiction because of how the brain functions. Now, the issue with the study that is so obnoxious, but changes nothing about the conclusions. These researchers decided that factor one traits would automatically make psychopaths more reward seeking, therefore that will be a large driver in drug seeking behavior. Why? Because they say so. Not because there is any remote evidence of that, but rather they weighted the study to show this. In other words, they decided that this would be the case, and then upended the entirety of psychopathy in order to make their conclusion fit this assertion, despite it flying in the face of every neurobiological and genetic study done on psychopathy, ever.

Due to this frankly stupid decision, they concluded that factor two traits were what mitigated the drug craving and lack of withdrawal, but also that factor two traits are what are created by the difference in the brain, not factor one.

Let me explain why this is dumb as hell. Factor two traits are antisocial personality disorder. They have nothing to do with psychopathy. Psychopathy is related to all the brain differences, which has been demonstrated time and again through brain scans, on both antisocial and regular psychopaths. They have decided to ignore all of that research and shift the brain differences to factor two, rather than factor one. Let me clear this up real quick:

According to B. Karpman (1948), the primary psychopath can be described as:

The root disorder in patients diagnosed with it whereas secondary psychopathy was defined as an aspect of another psychiatric disorder or social circumstances. Today the primary psychopathy is considered to have mostly Factor 1 traits from the PCL-R (arrogance, callousness, manipulative, lying) whereas secondary psychopaths have a majority of Factor 2 traits (impulsivity, boredom proneness, irresponsibility, lack of long term goals).”(Karpman, 1948, p. 525) Other authors have noted that primary psychopathy is used “. . . to differentiate between psychopathy that is biological in origin and secondary psychopathy that results from a combination of genetic and environmental influences”

Furthermore:

According to Hare (1993), the distinguishing feature between a true psychopath and a sociopath is that psychopaths are born as psychopaths whereas sociopaths are the product of one’s developmental environment. G.E. Partridge (1930) used the term sociopathic personality to stress the importance of environmental influences. Partridge used this term“. . . to emphasis failure to conform to societal demands and pointed to the role of environmental or cultural factors in the etiology of behavioral deviance”(Sutker& Allain, 2001, p. 446).Hare notes that both personality disorders (psychopathy and sociopathy) are the result of an interaction between genetic predispositions and environmental factors, but psychopathy leans towards the hereditary whereas sociopathy tends toward the environmental.

In further distinguishing the difference between the terms psychopathy and sociopathy, Hare offers: The difference between sociopathy and psychopathy . . . often reflect the user’s views on the origins and determinants of the disorder. Most sociologists, criminologists and even some psychologists believe the disorder is caused by social conflicts and thus prefer the term sociopath. . . those who believe that a combination of psychological, biological, genetic and environmental factors all contribute to the disorder are more likely to use the term psychopath.(Hare,1993, p. 23)

Psychopathy, Antisocial Personality & Sociopathy: The Basics A History Review Paula M. MacKenzie, PsyD, MSEd

So… again you are making me defend Hare… seriously, stop it… Hare, who decided on the factor one versus factor two traits said, primary is genetic, and secondary (ASPD) is environmental, but may have genetic factors. Environment does not cause heritable changes in the brain, as primary psychopathy has. The changes in the brain are not related to factor two traits, but these researchers decided that was not the case, and turned the concept on its head to… I don’t know, redefine psychopathy? Make their conclusion fit their supposition instead of doing real science or read all the studies that directly contradict their presumptions? I have no idea what they are thinking here. Especially when you consider how rare psychopathy actually is, and how many people in prison qualify for a diagnosis of ASPD.

Psychopathy/antisocial personality disorder conundrum

As currently construed, the diagnosis of antisocial personality disorder grossly over-identifies people, particularly those with offence histories, as meeting the criteria for the diagnosis. For example, research shows that between 50% and 80% of prisoners meet the criteria for a diagnosis of antisocial personality disorder, yet only approximately 15% of prisoners would be expected to be psychopathic, as assessed by the PCL-R. As such, the characteristics and research findings drawn from the psychopathy research may not be relevant for those with antisocial or dissocial personality disorder.

By their argument, fifty to eighty percent of prisoners should be addiction immune, not fifteen percent (which is actually closer to 10-13%, but whatever). How is that an argument?

I can agree with the scientific conclusions. Psychopathy, specifically the changes in the brain and the difference in chemical processing, make psychopaths immune to addiction. This is backed up another neuroscientist that I had a conversation with over on Quora, which is relayed in two separate comments:

Unsurprisingly, the frontal lobe of psychopath functions differently than that of neurotypicals, subsequently causing psychopathic “cold-heartedness” etc. But it also is the reason why psychopaths are apparently immune to addiction - because the reduced frontal lobe involvement in the reward circuitry means that a psychopath in withdrawal from an addictive substance only feels it in the body, and not in the mind. Neurotypical addicts experience withdrawal symptoms with severe emotional suffering, which is indistinguishable from the physical pain/discomfort of withdrawal.

Meghan Hibicke

One characteristic of psychopathy is low frontal lobe activity. Coincidentally, the affected part of the brain is part of the reward pathway and heavily involved in addiction, and the subjective misery of withdrawal (from any addiction). So while a neurotypical person might experience heroin withdrawal as “I am dying; my life is over; even if I survive, I will be hopelessly in pain and misery forever,” psychopathic people might experience heroin withdrawal as “I feel sick, so will take some Zofran, drink some Pedialyte, and wait for this to be over.”

But like Athena Walker said, psychopaths don’t get much pleasure, reward, or feelings of contentment/safety from opiates due to their low frontal lobe activity. So psychopaths are unlikely to become physically dependent on heroin in the first place.

Meghan Hibicke

In the next post I will be going into how I see addiction based on a story of an active addict. I haven’t an interest in going through the rest of this one to have to sort out their decision to “control for” factor two, which effectively was, blame factor one, and redefine the causes of factor two, other than to debunk it, as it’s idiotic.

Next week should be interesting.