Addiction threshold levers — the incentive-sensitisation / reward-drive operating-point correction, decomposed into DNA-grounded levers (L3-dominant with L1+L2 engaged; the consolidated sensitisation-gain core named, out of reach — the second PARTIAL fit in the series)

Addiction's incentive-sensitisation substrate maps onto the threshold frame, loading most on the reward drive (L3, five genes) but engaging the glutamate (L1) and inhibitory (L2) levers too. It is the second partial fit: the dominant fault, a consolidated learned sensitisation gain, is named but out of reach. Targets ranked, never drugs; addiction is a treatable medical condition.

The plasticity-consolidation and state-switching chapters established addiction not as weakness but as incentive sensitisation: repeated exposure trains the reward circuit into a consolidated, low-threshold attractor whose reward gain persists after withdrawal — the engine of relapse and cue-reactivity. That consolidated gain is the discriminant — it is what makes addiction chronic, and it is a learned plastic trace, not an instantaneous set-point. This chapter applies the same piece of inherited technology the bipolar, epilepsy, depression, schizophrenia, autism and ADHD levers chapters used — the threshold-shift intervention logic from the analgesic reproducibility package (Zenodo 10.5281/zenodo.20733420), whose three abstract levers are L1 change the inward (excitatory) current, L2 change the outward (potassium / inhibitory) current, L3 change the up-stream drive — and it produces the second PARTIAL fit in the series. Addiction is the seventh distribution pattern, and the richest: it is L3-dominant with L1 and L2 both engaged. Of nine lever genes, five sit on the up-stream reward-drive lever (L3: SLC6A3 the dopamine transporter, DRD2 the D₂ receptor, OPRM1 the μ-opioid receptor, OPRK1 the κ-opioid receptor, and CHRNA5 the α5 nicotinic subunit), two on the inward glutamate-plasticity lever (L1: GRIN2A, GRIN2B), and two on the inhibitory-restore lever (L2: GABRG3, GABRA2). That engagement of L1 and L2 is the textural inverse of ADHD, which was L3-only with both ionic levers empty (“not a channelopathy”); addiction does recruit the ionic levers — a richer reachable surface where naltrexone, acamprosate and topiramate-type directions live (as directions, never doses). Yet the fit is still partial, for a precise and deeper reason than ADHD's. The reachable surface is the instantaneous drive/excitability axis (reached across L1, L2 and L3). But the dominant addiction fault is the consolidated sensitisation gain (SG axis) — the learned reward-circuit amplitude that drives chronicity — and it is doubly out of reach: it is a gain, not a fold (the ADHD lesson: a lever that moves a fold has no handle on an amplitude) and it is consolidated / learned — a plasticity (E0-layer) variable, not an instantaneous operating point a lever can shift at all. The SG axis is named with four real genes — the ΔFosB master switch FOSB, the neurotrophin BDNF, the transcription factor CREB1, and the synaptic-plasticity immediate-early gene ARC — carried with their own promoter reads alongside but not reached. So the fit is graded [L] partial, the second non-clean fit in the series, and it marks the convergence: addiction's out-of-reach axis is precisely the E0 plasticity layer — the point where the threshold-leverisation route meets the plasticity-dynamics route, and the lever frame names the learned trace out of reach honestly. Each gene is placed by reading its own promoter switch stiffness — γ = −mean nearest-neighbour stacking free energy (SantaLucia 1998) over its promoter window, turned into |h_sp| = spinodal(γ) with the frozen engine read-only — and six of the thirteen reads (SLC6A3, DRD2, GRIN2A, GRIN2B, GABRA2, BDNF from the depression / schizophrenia / autism caches) are carried over verbatim, with the seven opioid / nicotinic / plasticity genes live GRCh38 strand-aware reads. The DNA reads carry an inversion that is orthogonal to reach, not aligned with it as ADHD's was: the stiffest promoter in the set, the dopamine transporter SLC6A3 (|h_sp| ≈ 0.778), is a reachable lever, the softest, the μ-opioid receptor OPRM1 (|h_sp| ≈ 0.541), is also a reachable lever, and the out-of-reach gene ARC is the second-stiffest read in the whole set — so stiffness predicts neither reach nor priority. Three fail-closed disciplines ride along, and the forbidden-claim scanner adds three classes specific to this topic: a drug-seeking class (it rejects where-to-buy / how-to-obtain / inject / snort / get-high / euphoria / dealer vocabulary), a cure-miracle class (it rejects miracle-cure / guaranteed-sober / detox-miracle / addiction-gone framing), and a moral-framing class (it rejects moral-failing / just-stop framing), all negation-guarded. The firewall is absolute: the promoter |h_sp| is a gene's own switch stiffness, never a receptor occupancy, a synaptic dopamine / opioid level, a drug's potency, a dose, a clinical effect, and never the consolidated sensitisation gain itself. efficacy = 0; not medical advice; addiction is a treatable medical condition, not a moral failing; the hard problem stays open.

What §26 and §28 established (a reward gain, consolidated by plasticity)

The state-switching chapter and the plasticity-consolidation chapter did for addiction what the earlier disorder chapters did for their conditions: they refused the ‘weak will’ picture and replaced it with a statement about which kind of fault addiction is. The result is sharp, and it is the substrate the whole of this chapter rests on: addiction is incentive sensitisation — repeated exposure trains the reward circuit into a consolidated, low-threshold attractor whose reward gain persists after withdrawal. Two ideas carry the load. A reward drive — the instantaneous tone of dopaminergic, opioid and cholinergic signalling that sets where the reward set-point currently sits — is the surface where the established pharmacology acts. But the consolidated sensitisation gain — the learned amplitude that plasticity has written into the circuit, the trace that makes a cue re-ignite craving months into abstinence — is the dominant axis, and it is a different kind of variable entirely. §26 grounded this in the E0 plasticity layer: the gain is not a knob you turn but a memory the circuit has consolidated, and that consolidation is exactly what gives addiction its chronicity and its relapse signature. §28 placed addiction among the state-switching disorders: the sensitised attractor is a low-threshold state the system falls into and re-enters under cue or stress.

Those two chapters proved the substrate and stopped. They said addiction is a sensitised reward gain consolidated by plasticity, and that the gain persists after the drug is gone. They did not resolve that substrate into concrete levers on the operating point, name the genes each lever touches, place those genes by their own DNA, or — the point that makes this the second partial fit — ask honestly whether the cross-cutting threshold-shift logic can reach the dominant axis at all. A mechanism atlas should be able to say which molecular targets realise the reachable correction and be honest, by name, about the axis the lever frame cannot touch. That is exactly what this chapter does — and as with ADHD, the honest answer is that the frame catches one axis and misses the dominant one. Unlike ADHD, the axis it misses is not merely a different surface but a different layer: a learned, consolidated trace that lives in the plasticity dynamics, not in any instantaneous fold.

The inherited technology, applied a seventh time — and the L3-dominant-with-L1/L2 pattern

The handle is not invented here. It is the same threshold-shift intervention logic the bipolar, epilepsy, depression, schizophrenia, autism and ADHD chapters inherited from the analgesic reproducibility package (Zenodo 10.5281/zenodo.20733420). Its premise is general: an operating point is set by a balance of currents and the drives that bias them, so there are exactly three levers on it. L1 — change the inward, excitatory current. L2 — change the outward, repolarising (or inhibitory) current. L3 — change the up-stream drive that sets where the operating point sits. The frame applies unchanged because the addiction substrate, the six prior levers chapters, and the analgesic package all share the same R19 substrate — the engine's supercritical pitchfork ṣ = g·s − s³ + h, whose spinodal fold IS the switching barrier. Nothing about the engine is touched; the module re-emerges the frozen tree read-only, confirms it byte-unchanged, and registers as the fourteenth atlas citizen (ADD-T-L).

Addiction is the seventh distribution pattern across the series, and the richest reachable surface yet. Where bipolar leaned on L1 (calcium channels), epilepsy on L1+L2 (the M-current), depression on L3 (the up-stream HPA / monoamine / neurotrophic drives, with a reachable L1/L2 mix), schizophrenia on L1+L3 co-dominantly, autism on L1-dominant with a sparse L3, and ADHD on L3-only (with L1 and L2 both empty), addiction is L3-dominant with L1 and L2 both present: of nine lever genes, five sit on L3 (the up-stream reward drive), two on L1 (the glutamate-plasticity substrate), and two on L2 (the inhibitory-restore axis). This is the textural inverse of ADHD. ADHD's emptiness on L1 and L2 was a positive statement — it is not a channelopathy — whereas addiction recruits the ionic levers: the glutamatergic plasticity substrate where an acamprosate / N-acetylcysteine direction lives, and the GABAergic restore axis where a topiramate-type direction lives. Addiction's actionable biology is broader than ADHD's, spanning the reward-drive transporters and receptors and the ionic machinery. The pipeline is reused at the level of code, not analogy: six of the thirteen reads — SLC6A3 and DRD2 on the drive side, GRIN2A, GRIN2B, GABRA2 on the ionic side, and BDNF on the out-of-reach side — are carried over verbatim from the depression, schizophrenia and autism caches, because γ is a strand-symmetric property of the sequence and does not change between problems; the seven opioid, nicotinic and plasticity genes (OPRM1, OPRK1, CHRNA5, GABRG3, FOSB, CREB1, ARC) are fetched fresh (GRCh38, strand-aware).

The second partial fit: why the dominant axis is doubly out of reach (deeper than ADHD's)

This is the result that makes addiction the most structurally honest chapter since ADHD, and the second that does not produce a clean fit. The module says so in a partial-fit witness that grades the fit [L] partial and records it as the second partial fit in the series. The reachable side is genuine and broad: the lever frame reaches the instantaneous drive / excitability operating point across all three levers — the L3 reward drive, the L1 glutamate-plasticity substrate, and the L2 inhibitory restore — exactly where the established addiction pharmacology acts. But the dominant addiction fault is the consolidated sensitisation gain (SG axis), and it sits out of reach for a reason that is deeper than ADHD's, and doubly so. The first sense is the ADHD lesson, inherited intact: the SG axis is a gain, not a fold. ADHD was the first partial fit because its dominant gain-amplitude axis (synthesis, release) was out of reach — a drive-tone lever has no handle on how much transmitter is made; a fold does not set a gain. Addiction's dominant axis is also a gain — the learned reward-circuit amplitude — and so it inherits ADHD's out-of-reach verdict for the same mechanical reason. The second sense is new and is what makes addiction's partiality deeper: the SG gain is consolidated / learned — a plasticity (E0-layer) variable, a trace written into the circuit over time, not an instantaneous operating point that any lever (drive or ionic) can shift at all. ADHD's gain was at least an instantaneous amplitude; addiction's gain is a memory. So the SG axis is out of reach twice over: as a gain (not a fold) and as a learned trace (not an instantaneous variable). Either way the conclusion is the same: [L], not [V]. The partial grade is the finding, not a failure — it marks exactly where the cross-cutting threshold logic does and does not apply, and it refuses to manufacture a clean fit on a biology whose core is a consolidated plastic trace rather than a threshold.

The second strengthening is the convergence, and it is the cleanest way to state what addiction adds to the series. Addiction's out-of-reach SG axis is not a vague ‘everything else’ — it is precisely the E0 plasticity layer. The threshold-leverisation route (the one this whole series has pursued: decompose an operating point into instantaneous levers) and the plasticity-dynamics route (the one §26 opened: how the circuit consolidates a trace over time) meet here, at the addiction SG axis. The lever frame reaches the instantaneous reward drive; the consolidated gain belongs to the dynamics route; and addiction is the disorder where those two routes touch. The honest move — and the one this chapter makes — is for the threshold frame to name the learned trace out of reach rather than pretend an instantaneous lever can move a consolidated memory. The module captures all of this in a domain-restriction witness (INSTANT = reached across L1/L2/L3, SG = named but not reached) and an out-of-reach-targets section that lists the four plasticity-trace genes by name — making the partiality concrete, axis-structured and gene-named rather than a vague hedge, and marking the precise seam where the two routes converge.

L3 is the core — five reward-drive levers (addiction pharmacology as directions)

The largest reachable lever is the up-stream reward drive, and it carries five genes — the transporters and receptors that set the tone of dopaminergic, opioid and cholinergic reward signalling. SLC6A3 is the dopamine transporter (DAT), the reuptake pump that sets ambient dopamine tone in the reward pathway — carried here as a drive-tone node, and the direction associated with the dopaminergic antidepressant / smoking-cessation agent bupropion. DRD2 is the D₂ dopamine receptor (the Taq1A reward-sensitivity locus), the receptor that reads dopaminergic reward drive — carried over from the schizophrenia cache as a reward-tone node. OPRM1 is the μ-opioid receptor, the principal opioid reward receptor and the naltrexone direction (an antagonist arm used across opioid and alcohol use). OPRK1 is the κ-opioid receptor, the dysphoria / anti-reward arm whose modulation is a distinct reward-tone direction. And CHRNA5 is the α5 nicotinic acetylcholine receptor subunit, the nicotine-reward locus and the varenicline direction. These map five real-world pharmacological routes — the dopaminergic, the μ- and κ-opioid, and the nicotinic — onto the reward-drive lever as directions on a lever, never as doses, drugs, or recommendations.

The crucial discipline is the one the whole frame turns on: a promoter read places a gene on a lever; it says nothing about whether raising or lowering that gene's activity is the therapeutic direction, or how far is too far, or in whom. Every one of the five reward-drive links is graded [O] cited biology, never derived from the substrate. And the reward-drive levers carry the same built-in honesty ADHD's did: a drive-tone lever modulates the instantaneous tone of reward signalling, which is a real and reachable handle, but it does not reach down into the consolidated gain that plasticity has written into the circuit — the dominant fault and the subject of a later section. So the reward-drive levers are genuine, actionable directions on the reachable instantaneous axis, and they are explicitly not a claim to have reached addiction's learned core. A direction, never a dose — and the agents are named as a sign on a lever, never as something to obtain or use. efficacy = 0.

L1 and L2 engaged — the glutamate-plasticity and inhibitory-restore levers (the ADHD inverse)

What separates addiction's reachable surface from ADHD's is that the ionic levers are not empty. The inward lever L1 carries two glutamate-plasticity genes. GRIN2A and GRIN2B are the NMDA-receptor 2A and 2B subunits — the glutamatergic machinery through which the reward circuit's synaptic plasticity is induced, and the substrate where an acamprosate / N-acetylcysteine-type glutamate-normalising direction acts. They are carried over verbatim from the autism cache, because γ is strand-symmetric and identical between problems. The outward lever L2 carries two inhibitory-restore genes. GABRG3 and GABRA2 are GABA_A-receptor subunits — the inhibitory machinery whose restoration is a topiramate-type direction (GABRA2 in particular carries a well-known alcohol-dependence GWAS signal, and is carried over verbatim from the autism cache). So addiction engages all three lever classes on its reachable instantaneous surface: the reward drive (L3), the glutamatergic plasticity substrate (L1), and the GABAergic restore axis (L2).

This is the textural inverse of ADHD, and the contrast is the cleanest way to see what addiction's engagement means. ADHD was L3-only — the ionic levers empty, ‘not a channelopathy’ — and that emptiness was the finding. Addiction recruits L1 and L2: there is a glutamatergic plasticity substrate and a GABAergic restore axis a lever can touch, so the reachable surface is richer than ADHD's. And yet — this is the point — addiction is still a partial fit. A broader reachable surface does not make the fit clean, because the dominant fault is not on any of the three instantaneous levers at all. ADHD missed its dominant axis because that axis was a gain on a different surface; addiction misses its dominant axis because that axis is a consolidated gain on a different layer — the learned plasticity trace. Each of the four ionic links is graded [O] cited biology, never derived; the glutamate and GABA directions are genuine handles on the instantaneous reward-circuit excitability, and they are explicitly not a handle on the consolidated trace. Engaging L1 and L2 widens what the frame reaches; it does not let the frame reach the dominant fault.

The out-of-reach SG axis: ΔFosB, CREB, ARC, BDNF — and the convergence with the E0 layer

The dominant addiction fault is the consolidated sensitisation gain (SG) axis — the learned reward-circuit amplitude that plasticity has written in — and it is exactly the axis the instantaneous levers cannot reach. The module names it with four real genes, each carried with its own promoter read alongside but explicitly not a lever. FOSB is the gene of ΔFosB, the unusually stable transcription-factor isoform that accumulates with repeated exposure and is the canonical master switch of the consolidated addiction trace — the molecular embodiment of the learned gain. CREB1 is the cAMP-response-element-binding protein, the transcription factor through which reward signalling is consolidated into lasting change. ARC is the activity-regulated cytoskeleton-associated immediate-early gene, a core effector of synaptic plasticity and consolidation. And BDNF is brain-derived neurotrophic factor, the neurotrophin that drives the structural plasticity underlying the sensitised circuit — carried over verbatim from the depression cache. Together these four are the plasticity trace: the consolidated, learned amplitude that makes addiction chronic.

None of these is a lever, and the reason is the doubled one from the partial-fit section: the SG gain is a gain, not a fold (no instantaneous lever sets an amplitude), and it is a consolidated, learned trace (it lives in the plasticity dynamics, not in any instantaneous operating point). This is the direct analogue of ADHD's named-out-of-reach gain axis, named here under the same discipline — out-of-reach axes are carried on the map, by name, with real genes, so the partiality is concrete rather than hand-waved — but extended to a learned gain. And it is the precise point of convergence the whole chapter builds toward: the SG axis is the E0 plasticity layer. The threshold-leverisation route (decompose into instantaneous levers) reaches the instantaneous reward drive; the consolidated gain belongs to the plasticity-dynamics route; and addiction is the disorder where the two routes touch. The lever frame's honest contribution is to name the learned trace out of reach — to mark, by gene, the axis the instantaneous decomposition cannot move — rather than pretend a drive or ionic lever can rewrite a consolidated memory. Each of the four genes is graded [F] NOT REACHED for the lever frame (axis-structured, not dose-structured), with its promoter γ read carried alongside as [V] structural context only.

The DNA grounding: a promoter's own switch stiffness, and a decoupling orthogonal to reach

What places each of the thirteen genes — the five reward-drive levers, the two glutamate levers, the two GABA levers, and the four out-of-reach plasticity genes — is not a list but a read. For every gene, the module takes its promoter window (transcription start −2000 to +500 bases, Homo sapiens) and computes γ = −mean of the nearest-neighbour base-stacking free energies along that window (the SantaLucia 1998 nearest-neighbour thermodynamics), then turns that γ into the promoter's switch stiffness through the frozen engine's own functions: |h_sp| = spinodal(γ) = 2(γ/3)^1.5 and barrier = γ²/4. The reads span a real range. The five reward-drive levers, stiffest to softest, are the dopamine transporter SLC6A3 at γ ≈ 1.598 (|h_sp| ≈ 0.778, the stiffest in the whole set), the D₂ receptor DRD2 (γ ≈ 1.481, |h_sp| ≈ 0.694), the κ-opioid receptor OPRK1 (γ ≈ 1.435, |h_sp| ≈ 0.662), the α5 nicotinic subunit CHRNA5 (γ ≈ 1.425, |h_sp| ≈ 0.655), and the μ-opioid receptor OPRM1 (γ ≈ 1.255, |h_sp| ≈ 0.541, the softest in the whole set). The two L1 glutamate levers read GRIN2A at γ ≈ 1.470 (|h_sp| ≈ 0.686) and GRIN2B (γ ≈ 1.361, |h_sp| ≈ 0.611); the two L2 GABA levers read GABRG3 at γ ≈ 1.467 (|h_sp| ≈ 0.684) and GABRA2 (γ ≈ 1.372, |h_sp| ≈ 0.619). And the four out-of-reach plasticity genes read ARC at γ ≈ 1.580 (|h_sp| ≈ 0.764, the second-stiffest in the whole set), CREB1 (γ ≈ 1.529, |h_sp| ≈ 0.728), FOSB (γ ≈ 1.437, |h_sp| ≈ 0.663), and BDNF (γ ≈ 1.435, |h_sp| ≈ 0.662).

That range tells a story, and it is different from ADHD's in an instructive way. ADHD's reads carried a clean inversion: promoter stiffness ran opposite to reachability (the stiffest read was a reachable lever, the softest an out-of-reach gene). Addiction's reads carry no such alignment at all — stiffness is orthogonal to reach. The stiffest promoter in the set, the dopamine transporter SLC6A3 (|h_sp| ≈ 0.778), is a reachable reward-drive lever; the softest, the μ-opioid receptor OPRM1 (|h_sp| ≈ 0.541), is also a reachable lever (the naltrexone direction); and the second-stiffest, the plasticity gene ARC (|h_sp| ≈ 0.764), is out of reach. Reachable genes occupy both ends of the stiffness range, and an out-of-reach gene sits near the top — so promoter stiffness predicts neither which axis a gene is on nor its priority. That orthogonality is itself the cleanest demonstration of the firewall: if stiffness drove anything, this scatter could not occur. These are read on the same R19 substrate, with the same engine, that the bipolar, epilepsy, depression, schizophrenia, autism, ADHD and analgesic packages used — one substrate, one pipeline, now seven problems. And the γ read is a property of the gene's promoter sequence, blind to whether the gene is on or off and to gain / loss / expression level — that is all it is, and it is the reason the next section's ranking can carry γ alongside every target without ever letting it touch the score.

Ranking targets, the addiction unmet-need signature, and the firewall that adds three guards

The last component prioritises, and it prioritises targets, never drugs or doses. The addiction ranking spans all thirteen genes (the nine levers and the four out-of-reach plasticity genes), precisely so the partiality is visible in the ranking itself. A burden-weighted score combines three declared, cited weights — clinical burden (0.40), unmet need (0.35), and genetic-evidence / druggability (0.25) — on cited 1–5 tiers. The addiction signature is that the top of the ranking is non-actionable. The highest-scoring target is FOSB at #1 — the ΔFosB master switch, an out-of-reach plasticity gene — and the SG genes cluster at the top (FOSB #1, ARC #3, BDNF #4, CREB1 #5), because they carry the highest burden and the highest unmet need: nothing selectively reaches the consolidated trace. They are flagged not actionable, because ranking a target you have already declared out of reach as a next step would be incoherent. The leading actionable target is the μ-opioid receptor OPRM1 at #2 — the naltrexone direction — the highest-ranked gene the lever frame can actually move. Addiction's unmet-need floor is set at 3, above ADHD's floor of 2, because even the reachable routes are only partially effective and relapse is high — the established pharmacology helps but does not resolve the consolidated trace, so unmet need stays elevated even where a lever exists.

The consequence is a ranking that itself encodes the partial fit: the highest-burden, highest-unmet targets are the out-of-reach plasticity genes, and the leading actionable target sits just below them. Where the unmet need is highest the target is unreachable (the consolidated gain), and where the target is reachable the unmet need is still only partly met (high relapse) — the signature of a disorder whose treatments work on the instantaneous reward drive while the dominant learned axis stays out of reach. This also produces the firewall made visible, as decoupling, and addiction's decoupling is starker than ADHD's because stiffness here is orthogonal to everything. The γ read is carried alongside each target as structural context but is never folded into the score: the stiffest promoter in the set, the dopamine transporter SLC6A3 (|h_sp| ≈ 0.778), sits at priority #9, near the bottom; and the top-priority target, the ΔFosB switch FOSB, has only the seventh-stiffest read. If promoter stiffness drove the ranking, neither target could sit where it does.

A fail-closed forbidden-claim scanner guards the whole package, and for addiction it adds three classes specific to a substance-use topic. The drug-seeking class rejects where-to-buy, how-to-obtain, inject, snort, get-high, euphoria and dealer vocabulary outright, because an addiction mechanism map must never read as a guide to obtaining or using any substance. The cure-miracle class rejects miracle-cure, guaranteed-sober, detox-miracle and addiction-gone framing, because addiction is chronic and relapsing and no lever direction cures it. The moral-framing class rejects moral-failing and just-stop framing, because addiction is a medical condition, not a failure of will. All three classes are negation-guarded — a sentence that rejects a frame is allowed, a sentence that asserts one fails the build — and each carries a planted self-test that must fire on its own bait, failing the build if it ever does not. The firewall must be stated once more in full: the promoter |h_sp| is a gene's own switch stiffness, and it is never equated with a receptor occupancy, a synaptic dopamine or opioid level, a drug's potency, a dose, an in-vivo selectivity, a clinical effect, or — the addiction-specific clause — the consolidated sensitisation gain itself (the learned reward-circuit amplitude, the ΔFosB trace). This module reproduces bit-for-bit with the engine byte-unchanged.

Discipline: a direction, never a dose — a treatable condition, not a moral failing

Everything here is an in-silico reading of promoter sequence and a frame for organising targets, not a clinical measure, a diagnosis, or a prescription. The model asserts mechanism directions and target placements — addiction's incentive-sensitisation substrate can be engaged through the up-stream reward-drive lever and, unlike ADHD, through the ionic levers too; these reward-drive, glutamate and GABA genes populate those levers; addiction loads most on L3 but engages L1 and L2; the map reaches the instantaneous drive / excitability axis across all three levers; the dominant consolidated-sensitisation-gain axis is named and out of reach — doubly, as a gain and as a learned trace; the fit is therefore the second [L] partial fit in the series, and the convergence with the E0 plasticity layer — and nothing about which agent acts on any lever, at what dose, in whom, whether any real compound changes anyone's condition, or that anyone should change anything. The agents named as directions (the naltrexone, acamprosate, topiramate, varenicline and bupropion arms) are illustrations of a sign on a reachable lever, never a recommendation, and the recorded structure — the dominant axis out of reach, the consolidated trace named but unreached — is there precisely because a generic lever placement is not a clinical direction. Real addiction is polygenic and heterogeneous, and its established pharmacology is only partially effective with high relapse — a partiality that is locked, not smoothed over.

Two stricter boundaries close the chapter. Addiction is a treatable medical condition — a disorder of a consolidated reward circuit — not a moral failing, not a failure of will, and not a deficit of character; the map ranks where a clean unmet mechanistic direction exists, and it does not assert that any direction treats, resolves, or cures addiction, nor that anyone should be judged for it. And nothing in the reward-circuit biology described here is a licence to obtain or use any substance: the map is a disorder-mechanism frame, the scanner rejects where-to-buy / get-high / dealer framing and miracle-cure / guaranteed-sober framing outright, and the agents named as directions are mechanism signs, never a route to a substance and never a promise of a cure. A promoter read and a lever assignment are mechanism boundaries, not a claim about the felt quality of craving or recovery (Axis-A firewall — consciousness_claim = 0, the hard problem stays open). This is not medical advice, not a diagnosis, not a treatment protocol, and not a cure. medium_efficacy_tested = 0; targets ranked, never drugs or doses; no drug-seeking, miracle-cure, or moral-failing framing; addiction is a treatable medical condition, not a failure of will.