URGENT NEED FOR AN ALTERNATIVE

URGENT NEED FOR AN ALTERNATIVE

the drug effect on behavior was exquisitely related to the schedule (of reinforcement, i.e. the behavior and its context/consequences) the schedule is, as it were, the score of the symphony These changes are sufficient to change the music profoundly, making slow themes into fast and soft interludes into loud, even though the drugs do not affect the symphony or the quality of the instruments. (Peter Dews, 1964)the drug effect on behavior was related to the schedule the schedule is, as it were, the score of the symphony. Drugs given to the orchestral organism affect the tempi of the themes and the relative predominance of different sections of the orchestra. These changes are sufficient to change the music profoundly, making slow themes into fast and soft interludes into loud, even though the drugs do not affect the symphony or the quality of the instruments. (Peter Dews, 1964)

1

Behavior is a sequence of doings that occur, of necessity, in time. The schedule (of reinforcement) establishes the temporal sequencing of events and largely determines the temporal patterning of the dependent behavior. The schedule and the behavior are dynamically related. Drugs affect the equilibrium points of various transient steady states.

The schedule is, as it were, the score of the symphony. Drugs given to the orchestral organism affect the tempi of the themes and the relative predominance of different sections of the orchestra. These changes are sufficient to change the music profoundly, making slow themes into fast and soft interludes into loud, even though the drugs do not affect the symphony or the quality of the instruments.(Peter Dews, Humors, Proc Am Philosophical Society 1964)the drug effect on behavior was related to the schedule the schedule is, as it were, the score of the symphony. Drugs given to the orchestral organism affect the tempi of the themes and the relative predominance of different sections of the orchestra. These changes are sufficient to change the music profoundly, making slow themes into fast and soft interludes into loud, even though the drugs do not affect the symphony or the quality of the instruments. (Peter Dews, 1964)

2FUNCTIONAL CONTEXTUAL PHARMACOLOGYFunctional contextual pharmacology uses methods and concepts from behavior analysis to explore and explain the behavioral effects of drugs. Behavior analysis is a unique natural science approach to the study of behavior developed by B. F. Skinner, but since then refined and clarified philosophically (Steven Hayes, Aaron Brownstein, Linda Hayes, Dermot Barnes-Holmes, Kelly Wilson, etc)Because functional contextualism forms the theoretical and methodological foundation of FC pharmacology, it deserves careful attention.Because contextual behavioral science is our foundation, likewise attentionThe following review may clarify possibilities, and some of the reasons for the assumptions of functional contextualism, the position taken, why our flag is planted just here.In contrast to the dead ends of reductive mechanistic biologism.Behavioral pharmacology uses methods and concepts from behavior analysis to explore and explain the behavioral effects of drugs. Behavior analysis is a unique natural science approach to the study of behavior developed by B. F. Skinner and refined and clarified philosophically since (Hayes S + L, Brownstein, Barnes-Holmes, Wilson)Because behavior analysis forms the theoretical and methodological foundation of behavioral pharmacology, it deserves careful attention.Because contextual behavioral science is our foundation, likewise attentionI hope the previous walk through of the issues has clarified possibilities, and some of the reasons for the assumptions we have made, the position we have stated, why our flag is planted just here.3Assumptions, coherence, effectiveness

Mentalistic/Cognitivistic PsychopharmacologyBehavioral PharmacologyCredit to Chad Drake for diagram4Kelly Wilson 2001- Functional ContextualismThe following are some key points and underlying assumptions of our case:1. Formulated constructs ought to be continuous with the events within the field of purported interest.2. The ultimate validity of constructs is reducible to the extent of improvement in orientation to the field of interest they provide (i.e., enhanced prediction and control [with precision, scope and depth]). 3. Constructs ought not be confused with the crude events with which the scientist interacts.

Some Notes on Theoretical Constructs. Kelly Wilson, International Journal of Psychology and Psychological Therapy 2001, Vol. 1, N 2, pp. 205-2155

64. Constructs are never attributed ontological validity as result of any operational successes, rather they are maintained as operationally valid. The extent of this validity may be assessed according to the metric described in proposition 2 (improvement in orientation to the field of interest prediction and control). 5. Divergence from the above will at best be superfluous and at worst will draw the investigators efforts in directions unfruitful to the advancement of a given field. Some Notes on Theoretical Constructs. Kelly Wilson 2001 International Journal of Psychology and Psychological TherapyKelly Wilson 2001 - FC made simple - 27

8i.e. but the realness of drugs, neurotransmitters etc ???Scientific laws (and statements about observed phenomena including drugs, fMRIs, neurones) ... specify or imply responses and consequences.They are not ... obeyed by nature but by men that deal effectively with nature. The formula s = 1/2 gt2 does not govern the behavior of falling bodies it governs those who correctly predict the position of falling bodies at given times. (BF Skinner, 1969, p. 141)9

10Can we talk ontologically workably, and not slip into ontological mechanism?Languaging depression / SSRI / fMRI finding of enhanced dorsolateral medial cortex activity can be continuous with observed client / client-clinician behavior/ verbal response / scientist response to instrument outputSaying SSRI etc may enhance precision, scope and depth of analysing contextually client verbal response/ effective scientist behavior to instrument output and applicability to other client behavior/experiments/aspects of experiment and other fields of interest i.e. success in workability

11Can we talk ontologically workably, and not slip into ontological mechanism?Naming SSRI ought not be confused with the crude constructs with which the clinician/ scientist is interacting i.e. client, clinician or scientist behavior in a contextdepression / SSRI / fMRI finding need not be given ontological validity, rather only effectiveness validity, i.e. improving prediction and influence of client / clinician / scientist behavior with precision, scope and depthDivergence from the above will be superfluous or harmfully distracting. SEE ANATOMY OF AN EPIDEMIC the failure of DSM of neurochemical theories the mainstream psychiatric field12

13Hank Robb Listserve 25 Sept 2010Life is between the trapeze barsThe problem is a non-unitary assumption.You can't really "prove" the non-dualistic approach except to point out all the messes and dead ends you end up with not taking it - "Maybe so," agree the dualists "But that is just how things are! The problems that flow from dualism are just too bad and it's just HOW THINGS ARE!From a functional contextualist view, in the end, there's nothing ontologically that you can "hang on to." Life (and science) is an "act of faith up in the air how it works for a chosen purpose

14Pragmatism or Realism a choiceMonistic/holistic

Contextualistic

Humility of only ever considering the work as something of use for a chosen purpose

i.e. truth is specifically defined as the usefulness regarding prediction and influence, with precision, scope and depth

Treatment / intervention utility of the strategy is built in to every aspect of the work; philosophy / basic science / clinical

Values must guide the scientific approachDualistic/pluralistic

Mechanistic, non-contextualistic

Nobility of discovery of the reality of the way the universe is truly constructed

i.e. truth being assumed to be what things are really like, an ever more accurate correspondence to the reality of things

Treatment / intervention utility of the strategy is a separate matter entirely requiring a subsequent research program

Values not needed this IS how things ARE15Integrating Psychological / Neurobiological Levels in Contextual Behavioral ScienceThe Psychological Level The study of whole organisms acting in and with a context considered historically and situationallyThe Neurobiological Level The study of the nervous system of organisms in reaction to external and internal events and in relation to behavior16Integrating psychological and neurobiological in CBS in ACT / BA / FAP clinical practiceThe dangers of moving across levels without care:Hiding ignorance in concrete knowledge at other levels of analysis we know what this scan / chemical etc doesThe appeal of reductionism thats why it changes behaviorThe possibilities of research / clinical behavior across levels of analysis:Seeing / acting clinically on consistent processes An integrated fabric of science and clinician practice17The Vision of Contextual Neuroscience= the vision of behavioral pharmacologyPlace neurobiological evidence inside a larger effortunderstanding situated actions of whole organisms, focusing on the depth of psychological processes known to be importantIncluding especially transformative human verbal processes, i.e. arbitrarily applicable derived relational responding RFT= leaving the animal lab for behav pharma ???

18Assumptions, coherence, effectiveness

Mentalistic/Cognitivistic PsychopharmacologyBehavioral PharmacologyCredit to Chad Drake for diagram19

20Environmental influence on lethality of heroin in rats and humansLethality of large dose of heroin in 3 groups of rats:2 groups made dependent/tolerant over 30 days, and 1 control group2 different environments animals colony, and white noise room.

15mg/kg then given to all 3 groups and results as follows:96% lethality - Control group64% lethality - Novel environment to that of tolerance 32% lethality - Same environment as that of tolerance

21Environmental influence on lethality of heroin in rats and humans

Siegel et al. 1982 Heroin overdose death: Contribution of drug-associated Environmental cues. Science.22The situational specificity of toleranceImplicated in unexpected overdose deaths due to: OpioidsAlcoholPentobarbitalRelevant to understanding and preventing enigmatic overdoses in clinical practice.Eg - In the present study, all three overdose deaths could reflect this mechanism, as it is unlikely that these patients normally injected on staircases or public house toilets.

Deaths of heroin users in a general practice population. Bucknall and Robertson, J R Coll Gen Pract. 198623Animal model antipsychotic screeningPole climbing procedure - rats placed in a chamber with metal grid floor that can be electrified. A wooden pole protrudes upward from the floor. Occasionally, a tone sounds for a brief period, after which a shock is delivered to the grid. The rat canescape from the shock by climbing the pole after the shock starts, or avoid it by climbing during the tone. Neuroleptics interfere with avoidance responding at doses that do not affect escape responding; other drug classes fail to do so.An early, and well known, animal model used to screen drugs for antipsychotic properties is the pole-climbing (or pole-jump) escape/avoidance procedure. In this assay, rats are placed in a chamber with a metal grid floor that can be electrified. A wooden pole protrudes upward from the floor. Occasionally, a tone sounds for a brief period, after which a shock is delivered to the grid. The rat can escape from the shock by climbing the pole after the shock starts, or avoid it by climbing during the tone. Neuroleptics interfere with avoidance responding at doses that do not affect escape responding; other drug classes fail to do so. (This is an oversimplification, but aptly captures the rationale of the procedure.) The success of the escape-avoidance conditioning paradigm for screening neuroleptics initiated a search for assays selectively affected by other drug classes. This search was rather successful, and animal models continue to play an important in drug houses screening and evaluation of newly synthesized compounds (Porsolt, McArthur, & Lengre, 1993). For example, drug self-administration procedures involving nonhumans are typically employed in initial evaluations of the abuse potential of drugs being considered for clinical application (see Thompson & Unna, 1977).

24Pole-jump procedure drive-reduction i.e. cognitivist vs behavioral interpretationsUsual interpretation was chlorpromazine selectively decreased fear and anxiety without altering response to pain.Emphasis on functional control rather than hypothetical motivational constructs - Dews and Morse 1961Differences in the stimulus control over the avoidance and escape behaviors escape under a high stimulus control by shock (high probability in presence of shock) avoidance behavior under weaker discriminative control (relatively lower probability of occurrence compared to the escape)Behavioral mechanism of action of chlorpromazine was to decrease stimulus controlIn reviewing progress in behavioral pharmacology, Dews and Morse (1961) focused some attention on the finding by Courvoisier et al. (1953) that chlorpromazine had selective effects on avoidance responding. The widespread interpretation of the study was that chlorpromazine selectively decreased fear and anxiety without altering the response to pain. With an alternative emphasis on the functional control over the behavior rather than hypothetical motivational constructs, Dews and Morse focused on differences in the stimulus control over the avoidance and escape behaviors. The escape behavior was under a high degree of stimulus control by the electric shock, as indicated by its relatively high probability in the presence of shock. In contrast, the avoidance behavior was said to be under weaker discriminative control based on its relatively lower probability of occurrence compared to the escape responses. Dews and Morse further suggested that if the behavioral mechanism of action of chlorpromazine was to decrease stimulus control, it would be predicted that the drug would alter behavior under relatively weaker discriminative control at lower doses than behavior under strong stimulus control, producing an apparently selective effect on the purported fear or anxiety motivation underlying the avoidance response.

25Pole-jump procedure behavioral interpretations - implicatonsDews and Morse commented on early interpretations of clinical efficacy of psychotherapeutic drugs based on an alleviation of fear and anxiety:Researchers have done so due to impression that they are useful clinically, especially in reducing the reactions to aversive stimuli and situations. However, few people consult physicians because their work has too much fascination for them, or because they enjoy their play too much; the people to whom the drugs are given most frequently are by no means a representative sample of the general population. The drugs might be just as effective in alleviating fascination and enjoyment. Dramatic effects of the drugs is in quieting manic psychotics in most of whom no reason to infer aversive stimulation as a cause of hyperactivity26Pole-jump procedure behavioral interpretations clinical implicationsBehavioral mechanism of action of chlorpromazine was to decrease stimulus control (= seroquel/zyprexa)Antipsychotics a who cares feeling David Healydetachment, less bothered, less distracted by internal dialogues, strange thoughts or intrusive imagery. Voices, thoughts or obsessions still present, but receded from centre stage..alleviating fascination and enjoyment negative symptoms?neuropharmacological-neurotoxic factors might be causing cognitive deficits in bipolar disorder patients.As few as 1/3 of BPD patients achieve full social and occupational functional recovery to their own premorbid levels. depressive episodes and lower functional recovery27Conditioned effects of drugs US + CSLethality of heroin in rats the situational specificity of toleranceConditioned immunosuppression demonstrated in ratsConditioned nausea in patients receiving chemotherapyNeedle freaks extensive IV users find injection itself pleasurableDRUGS ACQUIRE STIMULUS PROPERTIES THROUGH CONDITIONING, AND AFFECT B/H IN ABSENCE OF CONDITIONINGi.e. drugs are US and also CS and effects will change over time.DRUGS ARE STIMULI AND THEREFORE PRODUCE EFFECTS WHICH DIFFER AS A FUNCTION OF THE CONDITIONS UNDER WHICH THEY ARE, AND HAVE BEEN, ADMINISTERED28Rate-dependent drug effectsAmphetamines at low to moderate doses:Increase low-rate operant respondingReduce high-rate operant responding ADHD may be inattentive, others overactive.Dexamphetamine calms manic patients - temporarilyEffects of stimulants depends on the baseline level of activity of person to whom they are given. Dews lab 1950s showed these effectsParadoxical effects of psychomotor stimulants Robbins and Sahakian Neuropharmacology 1979

And intriguing- The effects of stimulants depends in significant part on the baseline level of activity of the person to whom they are given.

This is standard behavioral pharmacology stuff- powerful and largely forgotten in clinical land.

29Verbal behavior and drug effectsExperiment with instructions and nicotine altered behavioral responses to gum Hughes et al 1985 & 1989 Rules can significantly influence both the quantitative effects and qualitative effects of active drugs and placebosVerbal mediation learned behavior often plays a role in determining the effects of abused and other substancesHowever very few studies in this area and transformation of stimulus functions not considered by any researchers yet!

Drug behavioral effects are rarely simple, but are lawful!

30Verbal behavior and drug effects ACT &Substance Use DisordersFunctional assessment / treatment Kelly Wilsons work, books Understanding Behavior Disorders chapter Kathleen PalmAcceptance, defusion: altering context of aversive/strong appetitivesValues: bring longer term valued consequences into present momentSAC / CPM empowering all of above, and were all in this togetherAlso CRAFT, 12 Step, disulfiram, buprenorphine, naltrexone, etc.

An RFT enhanced behavioral model provides a unifying and experimentally testable approach.

31Research in Clinical Practice - ACBSThe Research in Clinical Practice Collaborative is designed to bridge the gap betweenclinical practice and applied science. Our mission is to help members gather data that informs clinical decision making and that contributes to research.Empower and support clinicians in utilizing research methodsDevelop procedures and routines to give session-by-session feedback to track both client progress and our own progress as therapists. Identify a list of questions that clinicians would like answers to so that treatment development and training prioritize these solutions. Develop strategies to collect and utilize effectiveness data to inform treatment development, protocol modification (examining mediators, moderators),increase efficiency, promote dissemination and training. Develop a set of practical tools.

Studies directed at comparing the effects of any treatment on behavior, whether the treatment is pharmacological, physiological or behavioral, are flawed if these comparisons are not conducted in a manner that is conducive to controlling for and assessing the importance of the environmental conditions under which the behavior occurs. Those conditions can assume an overwhelming importance in determining the behavioral outcome, and it is therefore indeed perilous to ignore them.

32Behavior-Analytic Drug Studies1). Studying, intensively, a few (usually fewer than five) participants with well defined characteristics.2). Using within-subject (e.g., multiple-baseline across participants, withdrawal) experimental designs.3). Defining target behaviors carefully and using direct and repeated measures to quantify them.4). Analyzing data through visual inspection of figures depicting each participant's responding, not inferential statistics comparing groups.5). Socially validating acceptability of goals, procedures, and results of intervention for clients and care providers. Social validation implies emphasis on clinical, not experimental or statistical, significance of obtained effectsOver the past two decades, several authors, including two of us, have contended that the methods characteristic of applied behavior analysis could be put to good use in evaluating pharmacological interventions (e.g., Poling & Cleary, 1986; Poling & Ehrhardt, 1999; Schroeder, 1985; Wysocki & Fuqua, 1982). In brief, these methods involve:1). Studying, intensively, a few (usually fewer than five) participants with well defined characteristics.2). Using within-subject (e.g., multiple-baseline across participants, withdrawal) experimental designs.3). Defining target behaviors carefully and using direct and repeated measures to quantify them.4). Analyzing data through visual inspection of figures depicting each participant's responding, not through inferential statistics comparing group performance.5). Socially validating the acceptability of the goals, procedures, and results of an intervention for clients and care providers. Social validation implies emphasis on the clinical, not experimental or statistical, significance of obtained effects.

But my patients are alreadytaking these medications

What am I then to do?How may I best serve them?When might these possible effects be of benefit to them?

Can the hexaflex help me here?Hmmm, help me speculate a little

So

Can we use hexaflex terms hesitantly place substances around and consider?

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