Transcript Functional Contextual Pharmacology #3

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)
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)
FUNCTIONAL CONTEXTUAL PHARMACOLOGY
Functional 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 attention
The 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.
Assumptions, coherence, effectiveness
Behavioral
Pharmacology
Mentalistic/Cognitivistic
Psychopharmacology
Kelly Wilson 2001- Functional Contextualism
The 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.
Kelly Wilson 2001 - FC made simple - 2
4. 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
investigator’s 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 Therapy
i.e. but… the “realness” of drugs,
neurotransmitters etc ???
Scientific laws (and statements about observed
phenomena including drugs, fMRI’s, 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)
Can we talk ontologically workably, and
not slip into ontological mechanism?
1.
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 output
2.
Saying “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
Can we talk ontologically workably, and
not slip into ontological mechanism?
3.
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 context
4.
“depression” / “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 depth
5.
Divergence from the above will be superfluous or
harmfully distracting….
 SEE ANATOMY OF AN EPIDEMIC… the failure of DSM… of
neurochemical theories… the mainstream psychiatric field
Hank Robb – Listserve 25 Sept 2010
“Life is between the trapeze bars”
The 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
Pragmatism or “Realism” – a choice
Monistic/holistic
Dualistic/pluralistic
Contextualistic
Mechanistic, non-contextualistic
Humility of only ever considering the work
as something of use for a chosen purpose
Nobility of discovery of the reality of the
way the universe is truly constructed
i.e. truth is specifically defined as the
usefulness regarding prediction and
influence, with precision, scope and depth
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 built in to every aspect of the
work; philosophy / basic science / clinical
Treatment / intervention utility of the
strategy is a separate matter entirely
requiring a subsequent research program
Values must guide the scientific approach
Values not needed – this IS how things ARE
Integrating Psychological / Neurobiological
Levels in Contextual Behavioral Science
The Psychological Level
The study of whole organisms acting in and with a
context considered historically and situationally
The Neurobiological Level
The study of the nervous system of organisms in
reaction to external and internal events and in
relation to behavior
Integrating psychological and neurobiological
in CBS  in ACT / BA / FAP clinical practice
The dangers of moving across levels without care:
1.
Hiding ignorance in concrete knowledge at other levels of
analysis – “we ‘know’ what this scan / chemical etc does”
2.
The appeal of reductionism – “that’s ‘why’ it changes behavior”
The possibilities of research / clinical behavior across levels of
analysis:
1.
Seeing / acting clinically on consistent processes
2.
An integrated fabric of science and clinician practice
The Vision of Contextual Neuroscience
= the vision of behavioral pharmacology
Place neurobiological evidence inside a larger effort
understanding situated actions of whole organisms,
focusing on the depth of psychological processes
known to be important
Including especially transformative human verbal
processes, i.e. arbitrarily applicable derived
relational responding  RFT
= leaving the animal lab for behav pharma ???
Assumptions, coherence, effectiveness
Behavioral
Pharmacology
Mentalistic/Cognitivistic
Psychopharmacology
Environmental influence on
lethality of heroin in rats – and humans
Lethality of large dose of heroin in 3 groups of rats:
2 groups made dependent/tolerant over 30 days, and 1 control group
2 different environments – animal’s colony, and “white noise” room.
15mg/kg then given to all 3 groups and results as follows:
96% lethality - Control group
64% lethality - Novel environment to that of tolerance
32% lethality - Same environment as that of tolerance
Environmental influence on
lethality of heroin in rats – and humans
Siegel et al. 1982 “Heroin ‘overdose’ death:
Contribution of drug-associated Environmental cues.” Science.
The situational specificity of tolerance
Implicated in unexpected overdose deaths due to:
1.
Opioids
2.
Alcohol
3.
Pentobarbital
Relevant 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. 1986
Animal model antipsychotic screening
Pole 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 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.
Pole-jump procedure – “drive-reduction” i.e.
cognitivist vs behavioral interpretations
Usual 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 1961
Differences 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 control
Pole-jump procedure – behavioral
interpretations - implicatons
Dews 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 hyperactivity
Pole-jump procedure – behavioral
interpretations – clinical implications
Behavioral mechanism of action of chlorpromazine was to
decrease stimulus control (= seroquel/zyprexa)
Antipsychotics – a “who cares” feeling – David Healy
“…detachment, 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 recovery”
Conditioned effects of drugs US + CS
Lethality of heroin in rats – the situational specificity of tolerance
Conditioned immunosuppression demonstrated in rats
Conditioned nausea in patients receiving chemotherapy
“Needle freaks” – extensive IV users find injection itself pleasurable
DRUGS ACQUIRE STIMULUS PROPERTIES THROUGH CONDITIONING,
AND AFFECT B/H IN ABSENCE OF CONDITIONING
i.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, ADMINISTERED
Rate-dependent drug effects
Amphetamines – at low to moderate doses:
Increase low-rate operant responding
Reduce high-rate operant responding
ADHD – may be inattentive, others overactive.
Dexamphetamine calms manic patients - temporarily
Effects of stimulants depends on the baseline level of
activity of person to whom they are given.
Dews lab 1950’s showed these effects
“Paradoxical effects of psychomotor stimulants”
Robbins and Sahakian Neuropharmacology 1979
Verbal behavior and drug effects
Experiment 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 placebos
Verbal mediation – learned behavior – often plays a role in
determining the effects of abused and other substances
However 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!
Verbal behavior and drug effects
 ACT &Substance Use Disorders
Functional assessment / treatment – Kelly Wilson’s work, books
Understanding Behavior Disorders chapter – Kathleen Palm
Acceptance, defusion: altering context of aversive/strong appetitives
Values: bring longer term valued consequences into present moment
SAC / CPM empowering all of above, and “we’re all in this together”
Also CRAFT, 12 Step, disulfiram, buprenorphine, naltrexone, etc.
An RFT enhanced behavioral model provides a unifying
and experimentally testable approach.
Research in Clinical Practice - ACBS
The Research in Clinical Practice Collaborative is designed to bridge
the gap between clinical practice and applied science.
Our mission is to help members gather data that informs clinical decision
making and that contributes to research.
1.
Empower and support clinicians in utilizing research methods
2.
Develop procedures and routines to give session-by-session feedback
to track both client progress and our own progress as therapists.
3.
Identify a list of questions that clinicians would like answers to so that
treatment development and training prioritize these solutions.
4.
Develop strategies to collect and utilize effectiveness data to inform
treatment development, protocol modification (examining mediators,
moderators),increase efficiency, promote dissemination and training.
5.
Develop a set of practical tools.
Behavior-Analytic Drug Studies
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 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 effects
But my patients are already
taking 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…